| anno_start anno_end anno_text entity_type sentence section | |
| 0 10 Structures evidence Structures of human ADAR2 bound to dsRNA reveal base-flipping mechanism and basis for site selectivity TITLE | |
| 14 19 human species Structures of human ADAR2 bound to dsRNA reveal base-flipping mechanism and basis for site selectivity TITLE | |
| 20 25 ADAR2 protein Structures of human ADAR2 bound to dsRNA reveal base-flipping mechanism and basis for site selectivity TITLE | |
| 26 34 bound to protein_state Structures of human ADAR2 bound to dsRNA reveal base-flipping mechanism and basis for site selectivity TITLE | |
| 35 40 dsRNA chemical Structures of human ADAR2 bound to dsRNA reveal base-flipping mechanism and basis for site selectivity TITLE | |
| 0 5 ADARs protein_type ADARs (adenosine deaminases acting on RNA) are editing enzymes that convert adenosine (A) to inosine (I) in duplex RNA, a modification reaction with wide-ranging consequences on RNA function. ABSTRACT | |
| 7 41 adenosine deaminases acting on RNA protein_type ADARs (adenosine deaminases acting on RNA) are editing enzymes that convert adenosine (A) to inosine (I) in duplex RNA, a modification reaction with wide-ranging consequences on RNA function. ABSTRACT | |
| 47 62 editing enzymes protein_type ADARs (adenosine deaminases acting on RNA) are editing enzymes that convert adenosine (A) to inosine (I) in duplex RNA, a modification reaction with wide-ranging consequences on RNA function. ABSTRACT | |
| 76 85 adenosine residue_name ADARs (adenosine deaminases acting on RNA) are editing enzymes that convert adenosine (A) to inosine (I) in duplex RNA, a modification reaction with wide-ranging consequences on RNA function. ABSTRACT | |
| 87 88 A residue_name ADARs (adenosine deaminases acting on RNA) are editing enzymes that convert adenosine (A) to inosine (I) in duplex RNA, a modification reaction with wide-ranging consequences on RNA function. ABSTRACT | |
| 93 100 inosine residue_name ADARs (adenosine deaminases acting on RNA) are editing enzymes that convert adenosine (A) to inosine (I) in duplex RNA, a modification reaction with wide-ranging consequences on RNA function. ABSTRACT | |
| 102 103 I residue_name ADARs (adenosine deaminases acting on RNA) are editing enzymes that convert adenosine (A) to inosine (I) in duplex RNA, a modification reaction with wide-ranging consequences on RNA function. ABSTRACT | |
| 108 118 duplex RNA structure_element ADARs (adenosine deaminases acting on RNA) are editing enzymes that convert adenosine (A) to inosine (I) in duplex RNA, a modification reaction with wide-ranging consequences on RNA function. ABSTRACT | |
| 178 181 RNA chemical ADARs (adenosine deaminases acting on RNA) are editing enzymes that convert adenosine (A) to inosine (I) in duplex RNA, a modification reaction with wide-ranging consequences on RNA function. ABSTRACT | |
| 25 29 ADAR protein_type Our understanding of the ADAR reaction mechanism, origin of editing site selectivity and effect of mutations is limited by the lack of high-resolution structural data for complexes of ADARs bound to substrate RNAs. ABSTRACT | |
| 60 72 editing site site Our understanding of the ADAR reaction mechanism, origin of editing site selectivity and effect of mutations is limited by the lack of high-resolution structural data for complexes of ADARs bound to substrate RNAs. ABSTRACT | |
| 151 166 structural data evidence Our understanding of the ADAR reaction mechanism, origin of editing site selectivity and effect of mutations is limited by the lack of high-resolution structural data for complexes of ADARs bound to substrate RNAs. ABSTRACT | |
| 184 189 ADARs protein_type Our understanding of the ADAR reaction mechanism, origin of editing site selectivity and effect of mutations is limited by the lack of high-resolution structural data for complexes of ADARs bound to substrate RNAs. ABSTRACT | |
| 190 198 bound to protein_state Our understanding of the ADAR reaction mechanism, origin of editing site selectivity and effect of mutations is limited by the lack of high-resolution structural data for complexes of ADARs bound to substrate RNAs. ABSTRACT | |
| 209 213 RNAs chemical Our understanding of the ADAR reaction mechanism, origin of editing site selectivity and effect of mutations is limited by the lack of high-resolution structural data for complexes of ADARs bound to substrate RNAs. ABSTRACT | |
| 22 40 crystal structures evidence Here we describe four crystal structures of the deaminase domain of human ADAR2 bound to RNA duplexes bearing a mimic of the deamination reaction intermediate. ABSTRACT | |
| 48 64 deaminase domain structure_element Here we describe four crystal structures of the deaminase domain of human ADAR2 bound to RNA duplexes bearing a mimic of the deamination reaction intermediate. ABSTRACT | |
| 68 73 human species Here we describe four crystal structures of the deaminase domain of human ADAR2 bound to RNA duplexes bearing a mimic of the deamination reaction intermediate. ABSTRACT | |
| 74 79 ADAR2 protein Here we describe four crystal structures of the deaminase domain of human ADAR2 bound to RNA duplexes bearing a mimic of the deamination reaction intermediate. ABSTRACT | |
| 80 88 bound to protein_state Here we describe four crystal structures of the deaminase domain of human ADAR2 bound to RNA duplexes bearing a mimic of the deamination reaction intermediate. ABSTRACT | |
| 89 101 RNA duplexes structure_element Here we describe four crystal structures of the deaminase domain of human ADAR2 bound to RNA duplexes bearing a mimic of the deamination reaction intermediate. ABSTRACT | |
| 6 16 structures evidence These structures, together with structure-guided mutagenesis and RNA-modification experiments, explain the basis for ADAR deaminase domain’s dsRNA specificity, its base-flipping mechanism, and nearest neighbor preferences. ABSTRACT | |
| 32 60 structure-guided mutagenesis experimental_method These structures, together with structure-guided mutagenesis and RNA-modification experiments, explain the basis for ADAR deaminase domain’s dsRNA specificity, its base-flipping mechanism, and nearest neighbor preferences. ABSTRACT | |
| 65 93 RNA-modification experiments experimental_method These structures, together with structure-guided mutagenesis and RNA-modification experiments, explain the basis for ADAR deaminase domain’s dsRNA specificity, its base-flipping mechanism, and nearest neighbor preferences. ABSTRACT | |
| 117 121 ADAR protein_type These structures, together with structure-guided mutagenesis and RNA-modification experiments, explain the basis for ADAR deaminase domain’s dsRNA specificity, its base-flipping mechanism, and nearest neighbor preferences. ABSTRACT | |
| 122 138 deaminase domain structure_element These structures, together with structure-guided mutagenesis and RNA-modification experiments, explain the basis for ADAR deaminase domain’s dsRNA specificity, its base-flipping mechanism, and nearest neighbor preferences. ABSTRACT | |
| 141 146 dsRNA chemical These structures, together with structure-guided mutagenesis and RNA-modification experiments, explain the basis for ADAR deaminase domain’s dsRNA specificity, its base-flipping mechanism, and nearest neighbor preferences. ABSTRACT | |
| 16 21 ADAR2 protein In addition, an ADAR2-specific RNA-binding loop was identified near the enzyme active site rationalizing differences in selectivity observed between different ADARs. ABSTRACT | |
| 31 47 RNA-binding loop structure_element In addition, an ADAR2-specific RNA-binding loop was identified near the enzyme active site rationalizing differences in selectivity observed between different ADARs. ABSTRACT | |
| 79 90 active site site In addition, an ADAR2-specific RNA-binding loop was identified near the enzyme active site rationalizing differences in selectivity observed between different ADARs. ABSTRACT | |
| 159 164 ADARs protein_type In addition, an ADAR2-specific RNA-binding loop was identified near the enzyme active site rationalizing differences in selectivity observed between different ADARs. ABSTRACT | |
| 85 89 ADAR protein_type Finally, our results provide a structural framework for understanding the effects of ADAR mutations associated with human disease. ABSTRACT | |
| 116 121 human species Finally, our results provide a structural framework for understanding the effects of ADAR mutations associated with human disease. ABSTRACT | |
| 0 3 RNA chemical RNA editing reactions alter a transcript’s genomically encoded sequence by inserting, deleting or modifying nucleotides. INTRO | |
| 15 24 adenosine residue_name Deamination of adenosine (A), the most common form of RNA editing in humans, generates inosine (I) at the corresponding nucleotide position. INTRO | |
| 26 27 A residue_name Deamination of adenosine (A), the most common form of RNA editing in humans, generates inosine (I) at the corresponding nucleotide position. INTRO | |
| 54 57 RNA chemical Deamination of adenosine (A), the most common form of RNA editing in humans, generates inosine (I) at the corresponding nucleotide position. INTRO | |
| 69 75 humans species Deamination of adenosine (A), the most common form of RNA editing in humans, generates inosine (I) at the corresponding nucleotide position. INTRO | |
| 87 94 inosine residue_name Deamination of adenosine (A), the most common form of RNA editing in humans, generates inosine (I) at the corresponding nucleotide position. INTRO | |
| 96 97 I residue_name Deamination of adenosine (A), the most common form of RNA editing in humans, generates inosine (I) at the corresponding nucleotide position. INTRO | |
| 6 7 I residue_name Since I base pairs with cytidine (C), it functions like guanosine (G) in cellular processes such as splicing, translation and reverse transcription. INTRO | |
| 24 32 cytidine residue_name Since I base pairs with cytidine (C), it functions like guanosine (G) in cellular processes such as splicing, translation and reverse transcription. INTRO | |
| 34 35 C residue_name Since I base pairs with cytidine (C), it functions like guanosine (G) in cellular processes such as splicing, translation and reverse transcription. INTRO | |
| 56 65 guanosine residue_name Since I base pairs with cytidine (C), it functions like guanosine (G) in cellular processes such as splicing, translation and reverse transcription. INTRO | |
| 67 68 G residue_name Since I base pairs with cytidine (C), it functions like guanosine (G) in cellular processes such as splicing, translation and reverse transcription. INTRO | |
| 48 51 RNA chemical A to I editing has wide-ranging consequences on RNA function including altering miRNA recognition sites, redirecting splicing and changing the meaning of specific codons. INTRO | |
| 80 103 miRNA recognition sites site A to I editing has wide-ranging consequences on RNA function including altering miRNA recognition sites, redirecting splicing and changing the meaning of specific codons. INTRO | |
| 50 56 humans species Two different enzymes carry out A to I editing in humans; ADAR1 and ADAR2. INTRO | |
| 58 63 ADAR1 protein Two different enzymes carry out A to I editing in humans; ADAR1 and ADAR2. INTRO | |
| 68 73 ADAR2 protein Two different enzymes carry out A to I editing in humans; ADAR1 and ADAR2. INTRO | |
| 0 4 ADAR protein_type ADAR activity is required for nervous system function and altered editing has been linked to neurological disorders such as epilepsy and Prader Willi Syndrome. INTRO | |
| 30 35 ADAR1 protein In addition, mutations in the ADAR1 gene are known to cause the autoimmune disease Aicardi-Goutieres Syndrome (AGS) and the skin disorder Dyschromatosis Symmetrica Hereditaria (DSH). INTRO | |
| 81 85 mRNA chemical Hyper editing has been observed at certain sites in cancer cells, such as in the mRNA for AZIN1 (antizyme inhibitor 1). INTRO | |
| 90 95 AZIN1 protein Hyper editing has been observed at certain sites in cancer cells, such as in the mRNA for AZIN1 (antizyme inhibitor 1). INTRO | |
| 97 117 antizyme inhibitor 1 protein Hyper editing has been observed at certain sites in cancer cells, such as in the mRNA for AZIN1 (antizyme inhibitor 1). INTRO | |
| 122 150 glioma-associated oncogene 1 protein However, hypo editing also occurs in cancer-derived cell lines exemplified by reduced editing observed in the message for glioma-associated oncogene 1 (Gli1). INTRO | |
| 152 156 Gli1 protein However, hypo editing also occurs in cancer-derived cell lines exemplified by reduced editing observed in the message for glioma-associated oncogene 1 (Gli1). INTRO | |
| 4 8 ADAR protein_type The ADAR proteins have a modular structure with double stranded RNA binding domains (dsRBDs) and a C-terminal deaminase domain (see Fig. 1a for hADAR2 domains). INTRO | |
| 48 83 double stranded RNA binding domains structure_element The ADAR proteins have a modular structure with double stranded RNA binding domains (dsRBDs) and a C-terminal deaminase domain (see Fig. 1a for hADAR2 domains). INTRO | |
| 85 91 dsRBDs structure_element The ADAR proteins have a modular structure with double stranded RNA binding domains (dsRBDs) and a C-terminal deaminase domain (see Fig. 1a for hADAR2 domains). INTRO | |
| 110 126 deaminase domain structure_element The ADAR proteins have a modular structure with double stranded RNA binding domains (dsRBDs) and a C-terminal deaminase domain (see Fig. 1a for hADAR2 domains). INTRO | |
| 144 150 hADAR2 protein The ADAR proteins have a modular structure with double stranded RNA binding domains (dsRBDs) and a C-terminal deaminase domain (see Fig. 1a for hADAR2 domains). INTRO | |
| 0 5 ADARs protein_type ADARs efficiently deaminate specific adenosines in duplex RNA while leaving most adenosines unmodified. INTRO | |
| 37 47 adenosines residue_name ADARs efficiently deaminate specific adenosines in duplex RNA while leaving most adenosines unmodified. INTRO | |
| 51 61 duplex RNA structure_element ADARs efficiently deaminate specific adenosines in duplex RNA while leaving most adenosines unmodified. INTRO | |
| 81 91 adenosines residue_name ADARs efficiently deaminate specific adenosines in duplex RNA while leaving most adenosines unmodified. INTRO | |
| 17 26 adenosine residue_name The mechanism of adenosine deamination requires ADAR to flip the reactive base out of an RNA double helix to access its active site. INTRO | |
| 48 52 ADAR protein_type The mechanism of adenosine deamination requires ADAR to flip the reactive base out of an RNA double helix to access its active site. INTRO | |
| 89 105 RNA double helix chemical The mechanism of adenosine deamination requires ADAR to flip the reactive base out of an RNA double helix to access its active site. INTRO | |
| 120 131 active site site The mechanism of adenosine deamination requires ADAR to flip the reactive base out of an RNA double helix to access its active site. INTRO | |
| 48 58 duplex RNA structure_element How an enzyme could accomplish this task with a duplex RNA substrate is not known. INTRO | |
| 20 24 ADAR protein_type Furthermore, how an ADAR deaminase domain contributes to editing site selectivity is also unknown, since no structures of ADAR deaminase domain-RNA complexes have been reported. INTRO | |
| 25 41 deaminase domain structure_element Furthermore, how an ADAR deaminase domain contributes to editing site selectivity is also unknown, since no structures of ADAR deaminase domain-RNA complexes have been reported. INTRO | |
| 57 69 editing site site Furthermore, how an ADAR deaminase domain contributes to editing site selectivity is also unknown, since no structures of ADAR deaminase domain-RNA complexes have been reported. INTRO | |
| 108 118 structures evidence Furthermore, how an ADAR deaminase domain contributes to editing site selectivity is also unknown, since no structures of ADAR deaminase domain-RNA complexes have been reported. INTRO | |
| 122 147 ADAR deaminase domain-RNA complex_assembly Furthermore, how an ADAR deaminase domain contributes to editing site selectivity is also unknown, since no structures of ADAR deaminase domain-RNA complexes have been reported. INTRO | |
| 56 61 human species To address these knowledge gaps, we set out to trap the human ADAR2 deaminase domain (aa299–701, hADAR2d) bound to different duplex RNAs and solve structures for the resulting complexes using x-ray crystallography. INTRO | |
| 62 67 ADAR2 protein To address these knowledge gaps, we set out to trap the human ADAR2 deaminase domain (aa299–701, hADAR2d) bound to different duplex RNAs and solve structures for the resulting complexes using x-ray crystallography. INTRO | |
| 68 84 deaminase domain structure_element To address these knowledge gaps, we set out to trap the human ADAR2 deaminase domain (aa299–701, hADAR2d) bound to different duplex RNAs and solve structures for the resulting complexes using x-ray crystallography. INTRO | |
| 88 95 299–701 residue_range To address these knowledge gaps, we set out to trap the human ADAR2 deaminase domain (aa299–701, hADAR2d) bound to different duplex RNAs and solve structures for the resulting complexes using x-ray crystallography. INTRO | |
| 97 104 hADAR2d mutant To address these knowledge gaps, we set out to trap the human ADAR2 deaminase domain (aa299–701, hADAR2d) bound to different duplex RNAs and solve structures for the resulting complexes using x-ray crystallography. INTRO | |
| 106 114 bound to protein_state To address these knowledge gaps, we set out to trap the human ADAR2 deaminase domain (aa299–701, hADAR2d) bound to different duplex RNAs and solve structures for the resulting complexes using x-ray crystallography. INTRO | |
| 125 136 duplex RNAs structure_element To address these knowledge gaps, we set out to trap the human ADAR2 deaminase domain (aa299–701, hADAR2d) bound to different duplex RNAs and solve structures for the resulting complexes using x-ray crystallography. INTRO | |
| 147 157 structures evidence To address these knowledge gaps, we set out to trap the human ADAR2 deaminase domain (aa299–701, hADAR2d) bound to different duplex RNAs and solve structures for the resulting complexes using x-ray crystallography. INTRO | |
| 192 213 x-ray crystallography experimental_method To address these knowledge gaps, we set out to trap the human ADAR2 deaminase domain (aa299–701, hADAR2d) bound to different duplex RNAs and solve structures for the resulting complexes using x-ray crystallography. INTRO | |
| 44 47 RNA chemical We then evaluated the importance of protein-RNA contacts using structure-guided mutagenesis and RNA-modification experiments coupled with adenosine deamination kinetics. INTRO | |
| 63 91 structure-guided mutagenesis experimental_method We then evaluated the importance of protein-RNA contacts using structure-guided mutagenesis and RNA-modification experiments coupled with adenosine deamination kinetics. INTRO | |
| 96 124 RNA-modification experiments experimental_method We then evaluated the importance of protein-RNA contacts using structure-guided mutagenesis and RNA-modification experiments coupled with adenosine deamination kinetics. INTRO | |
| 138 168 adenosine deamination kinetics experimental_method We then evaluated the importance of protein-RNA contacts using structure-guided mutagenesis and RNA-modification experiments coupled with adenosine deamination kinetics. INTRO | |
| 13 20 flipped protein_state Trapping the flipped conformation RESULTS | |
| 4 8 ADAR protein_type The ADAR reaction involves the formation of a hydrated intermediate that loses ammonia to generate the inosine-containing product RNA (for reaction scheme see Fig. 1b). RESULTS | |
| 103 110 inosine residue_name The ADAR reaction involves the formation of a hydrated intermediate that loses ammonia to generate the inosine-containing product RNA (for reaction scheme see Fig. 1b). RESULTS | |
| 130 133 RNA chemical The ADAR reaction involves the formation of a hydrated intermediate that loses ammonia to generate the inosine-containing product RNA (for reaction scheme see Fig. 1b). RESULTS | |
| 46 61 8-azanebularine chemical The covalent hydrate of the nucleoside analog 8-azanebularine (N) mimics the proposed high-energy intermediate (for reaction scheme see Fig. 1b). RESULTS | |
| 63 64 N chemical The covalent hydrate of the nucleoside analog 8-azanebularine (N) mimics the proposed high-energy intermediate (for reaction scheme see Fig. 1b). RESULTS | |
| 13 20 hADAR2d mutant For trapping hADAR2d bound to RNA for crystallography, we incorporated 8-azanebularine into duplex RNAs shown recently to be excellent substrates for deamination by hADAR2d (for duplex sequence see Fig. 1c) (for characterization of protein–RNA complex see Supplementary Fig. 1). RESULTS | |
| 21 29 bound to protein_state For trapping hADAR2d bound to RNA for crystallography, we incorporated 8-azanebularine into duplex RNAs shown recently to be excellent substrates for deamination by hADAR2d (for duplex sequence see Fig. 1c) (for characterization of protein–RNA complex see Supplementary Fig. 1). RESULTS | |
| 30 33 RNA chemical For trapping hADAR2d bound to RNA for crystallography, we incorporated 8-azanebularine into duplex RNAs shown recently to be excellent substrates for deamination by hADAR2d (for duplex sequence see Fig. 1c) (for characterization of protein–RNA complex see Supplementary Fig. 1). RESULTS | |
| 38 53 crystallography experimental_method For trapping hADAR2d bound to RNA for crystallography, we incorporated 8-azanebularine into duplex RNAs shown recently to be excellent substrates for deamination by hADAR2d (for duplex sequence see Fig. 1c) (for characterization of protein–RNA complex see Supplementary Fig. 1). RESULTS | |
| 71 86 8-azanebularine chemical For trapping hADAR2d bound to RNA for crystallography, we incorporated 8-azanebularine into duplex RNAs shown recently to be excellent substrates for deamination by hADAR2d (for duplex sequence see Fig. 1c) (for characterization of protein–RNA complex see Supplementary Fig. 1). RESULTS | |
| 92 103 duplex RNAs structure_element For trapping hADAR2d bound to RNA for crystallography, we incorporated 8-azanebularine into duplex RNAs shown recently to be excellent substrates for deamination by hADAR2d (for duplex sequence see Fig. 1c) (for characterization of protein–RNA complex see Supplementary Fig. 1). RESULTS | |
| 165 172 hADAR2d mutant For trapping hADAR2d bound to RNA for crystallography, we incorporated 8-azanebularine into duplex RNAs shown recently to be excellent substrates for deamination by hADAR2d (for duplex sequence see Fig. 1c) (for characterization of protein–RNA complex see Supplementary Fig. 1). RESULTS | |
| 240 243 RNA chemical For trapping hADAR2d bound to RNA for crystallography, we incorporated 8-azanebularine into duplex RNAs shown recently to be excellent substrates for deamination by hADAR2d (for duplex sequence see Fig. 1c) (for characterization of protein–RNA complex see Supplementary Fig. 1). RESULTS | |
| 40 44 Bdf2 chemical In addition, for one of these duplexes (Bdf2), we positioned the 8-azanebularine opposite either uridine or cytidine to mimic an A-U pair or A-C mismatch at the editing site creating a total of three different RNA substrates for structural studies (Fig. 1c). RESULTS | |
| 65 80 8-azanebularine chemical In addition, for one of these duplexes (Bdf2), we positioned the 8-azanebularine opposite either uridine or cytidine to mimic an A-U pair or A-C mismatch at the editing site creating a total of three different RNA substrates for structural studies (Fig. 1c). RESULTS | |
| 97 104 uridine residue_name In addition, for one of these duplexes (Bdf2), we positioned the 8-azanebularine opposite either uridine or cytidine to mimic an A-U pair or A-C mismatch at the editing site creating a total of three different RNA substrates for structural studies (Fig. 1c). RESULTS | |
| 108 116 cytidine residue_name In addition, for one of these duplexes (Bdf2), we positioned the 8-azanebularine opposite either uridine or cytidine to mimic an A-U pair or A-C mismatch at the editing site creating a total of three different RNA substrates for structural studies (Fig. 1c). RESULTS | |
| 129 130 A residue_name In addition, for one of these duplexes (Bdf2), we positioned the 8-azanebularine opposite either uridine or cytidine to mimic an A-U pair or A-C mismatch at the editing site creating a total of three different RNA substrates for structural studies (Fig. 1c). RESULTS | |
| 131 132 U residue_name In addition, for one of these duplexes (Bdf2), we positioned the 8-azanebularine opposite either uridine or cytidine to mimic an A-U pair or A-C mismatch at the editing site creating a total of three different RNA substrates for structural studies (Fig. 1c). RESULTS | |
| 141 142 A residue_name In addition, for one of these duplexes (Bdf2), we positioned the 8-azanebularine opposite either uridine or cytidine to mimic an A-U pair or A-C mismatch at the editing site creating a total of three different RNA substrates for structural studies (Fig. 1c). RESULTS | |
| 143 144 C residue_name In addition, for one of these duplexes (Bdf2), we positioned the 8-azanebularine opposite either uridine or cytidine to mimic an A-U pair or A-C mismatch at the editing site creating a total of three different RNA substrates for structural studies (Fig. 1c). RESULTS | |
| 161 173 editing site site In addition, for one of these duplexes (Bdf2), we positioned the 8-azanebularine opposite either uridine or cytidine to mimic an A-U pair or A-C mismatch at the editing site creating a total of three different RNA substrates for structural studies (Fig. 1c). RESULTS | |
| 210 213 RNA chemical In addition, for one of these duplexes (Bdf2), we positioned the 8-azanebularine opposite either uridine or cytidine to mimic an A-U pair or A-C mismatch at the editing site creating a total of three different RNA substrates for structural studies (Fig. 1c). RESULTS | |
| 4 11 hADAR2d mutant The hADAR2d protein (without RNA bound) has been previously crystallized and structurally characterized revealing features of the active site including the presence of zinc. RESULTS | |
| 21 38 without RNA bound protein_state The hADAR2d protein (without RNA bound) has been previously crystallized and structurally characterized revealing features of the active site including the presence of zinc. RESULTS | |
| 60 72 crystallized experimental_method The hADAR2d protein (without RNA bound) has been previously crystallized and structurally characterized revealing features of the active site including the presence of zinc. RESULTS | |
| 130 141 active site site The hADAR2d protein (without RNA bound) has been previously crystallized and structurally characterized revealing features of the active site including the presence of zinc. RESULTS | |
| 168 172 zinc chemical The hADAR2d protein (without RNA bound) has been previously crystallized and structurally characterized revealing features of the active site including the presence of zinc. RESULTS | |
| 16 41 inositol hexakisphosphate chemical In addition, an inositol hexakisphosphate (IHP) molecule was found buried in the core of the protein hydrogen bonded to numerous conserved polar residues. RESULTS | |
| 43 46 IHP chemical In addition, an inositol hexakisphosphate (IHP) molecule was found buried in the core of the protein hydrogen bonded to numerous conserved polar residues. RESULTS | |
| 101 116 hydrogen bonded bond_interaction In addition, an inositol hexakisphosphate (IHP) molecule was found buried in the core of the protein hydrogen bonded to numerous conserved polar residues. RESULTS | |
| 4 19 crystallization experimental_method For crystallization of hADAR2d-RNA complexes, we used both the wild type (WT) deaminase domain and a mutant (E488Q) that has enhanced catalytic activity. RESULTS | |
| 23 34 hADAR2d-RNA complex_assembly For crystallization of hADAR2d-RNA complexes, we used both the wild type (WT) deaminase domain and a mutant (E488Q) that has enhanced catalytic activity. RESULTS | |
| 63 72 wild type protein_state For crystallization of hADAR2d-RNA complexes, we used both the wild type (WT) deaminase domain and a mutant (E488Q) that has enhanced catalytic activity. RESULTS | |
| 74 76 WT protein_state For crystallization of hADAR2d-RNA complexes, we used both the wild type (WT) deaminase domain and a mutant (E488Q) that has enhanced catalytic activity. RESULTS | |
| 78 94 deaminase domain structure_element For crystallization of hADAR2d-RNA complexes, we used both the wild type (WT) deaminase domain and a mutant (E488Q) that has enhanced catalytic activity. RESULTS | |
| 101 107 mutant protein_state For crystallization of hADAR2d-RNA complexes, we used both the wild type (WT) deaminase domain and a mutant (E488Q) that has enhanced catalytic activity. RESULTS | |
| 109 114 E488Q mutant For crystallization of hADAR2d-RNA complexes, we used both the wild type (WT) deaminase domain and a mutant (E488Q) that has enhanced catalytic activity. RESULTS | |
| 49 95 X-ray diffraction data collection and solution experimental_method A description of the crystallization conditions, X-ray diffraction data collection and solution of the structures can be found in Online Methods. RESULTS | |
| 103 113 structures evidence A description of the crystallization conditions, X-ray diffraction data collection and solution of the structures can be found in Online Methods. RESULTS | |
| 13 16 RNA chemical Four protein-RNA combinations generated diffracting crystals that resulted in high-resolution structures (hADAR2d WT–Bdf2-U, hADAR2d WT–Bdf2-C, hADAR2d E488Q–Bdf2-C, hADAR2d E488Q–Gli1) (Table 1). RESULTS | |
| 52 60 crystals evidence Four protein-RNA combinations generated diffracting crystals that resulted in high-resolution structures (hADAR2d WT–Bdf2-U, hADAR2d WT–Bdf2-C, hADAR2d E488Q–Bdf2-C, hADAR2d E488Q–Gli1) (Table 1). RESULTS | |
| 94 104 structures evidence Four protein-RNA combinations generated diffracting crystals that resulted in high-resolution structures (hADAR2d WT–Bdf2-U, hADAR2d WT–Bdf2-C, hADAR2d E488Q–Bdf2-C, hADAR2d E488Q–Gli1) (Table 1). RESULTS | |
| 106 123 hADAR2d WT–Bdf2-U complex_assembly Four protein-RNA combinations generated diffracting crystals that resulted in high-resolution structures (hADAR2d WT–Bdf2-U, hADAR2d WT–Bdf2-C, hADAR2d E488Q–Bdf2-C, hADAR2d E488Q–Gli1) (Table 1). RESULTS | |
| 125 142 hADAR2d WT–Bdf2-C complex_assembly Four protein-RNA combinations generated diffracting crystals that resulted in high-resolution structures (hADAR2d WT–Bdf2-U, hADAR2d WT–Bdf2-C, hADAR2d E488Q–Bdf2-C, hADAR2d E488Q–Gli1) (Table 1). RESULTS | |
| 144 164 hADAR2d E488Q–Bdf2-C complex_assembly Four protein-RNA combinations generated diffracting crystals that resulted in high-resolution structures (hADAR2d WT–Bdf2-U, hADAR2d WT–Bdf2-C, hADAR2d E488Q–Bdf2-C, hADAR2d E488Q–Gli1) (Table 1). RESULTS | |
| 166 184 hADAR2d E488Q–Gli1 complex_assembly Four protein-RNA combinations generated diffracting crystals that resulted in high-resolution structures (hADAR2d WT–Bdf2-U, hADAR2d WT–Bdf2-C, hADAR2d E488Q–Bdf2-C, hADAR2d E488Q–Gli1) (Table 1). RESULTS | |
| 50 53 RNA chemical In each of these complexes, the protein binds the RNA on one face of the duplex over ~ 20 bp using a positively charged surface near the zinc-containing active site (Fig. 2, Supplementary Fig. 2a). RESULTS | |
| 137 164 zinc-containing active site site In each of these complexes, the protein binds the RNA on one face of the duplex over ~ 20 bp using a positively charged surface near the zinc-containing active site (Fig. 2, Supplementary Fig. 2a). RESULTS | |
| 10 22 binding site site The large binding site (1493 Å2 RNA surface area and 1277 Å2 protein surface area buried) observed for hADAR2d is consistent with recent footprinting studies. RESULTS | |
| 103 110 hADAR2d mutant The large binding site (1493 Å2 RNA surface area and 1277 Å2 protein surface area buried) observed for hADAR2d is consistent with recent footprinting studies. RESULTS | |
| 137 157 footprinting studies experimental_method The large binding site (1493 Å2 RNA surface area and 1277 Å2 protein surface area buried) observed for hADAR2d is consistent with recent footprinting studies. RESULTS | |
| 20 23 RNA chemical Both strands of the RNA contact the protein with the majority of these interactions mediated through the phosphodiester-ribose backbone near the editing site (Fig. 2c, Supplementary Fig. 2 b–d). RESULTS | |
| 145 157 editing site site Both strands of the RNA contact the protein with the majority of these interactions mediated through the phosphodiester-ribose backbone near the editing site (Fig. 2c, Supplementary Fig. 2 b–d). RESULTS | |
| 4 14 structures evidence The structures show a large deviation from A-form RNA conformation at the editing site (Fig. 2, Fig. 3, Supplementary Video 1). RESULTS | |
| 43 49 A-form structure_element The structures show a large deviation from A-form RNA conformation at the editing site (Fig. 2, Fig. 3, Supplementary Video 1). RESULTS | |
| 50 53 RNA chemical The structures show a large deviation from A-form RNA conformation at the editing site (Fig. 2, Fig. 3, Supplementary Video 1). RESULTS | |
| 74 86 editing site site The structures show a large deviation from A-form RNA conformation at the editing site (Fig. 2, Fig. 3, Supplementary Video 1). RESULTS | |
| 4 19 8-azanebularine chemical The 8-azanebularine is flipped out of the helix and bound into the active site as its covalent hydrate where it interacts with several amino acids including V351, T375, K376, E396 and R455 (Fig. 3a, Supplementary Fig. 3a). RESULTS | |
| 23 34 flipped out protein_state The 8-azanebularine is flipped out of the helix and bound into the active site as its covalent hydrate where it interacts with several amino acids including V351, T375, K376, E396 and R455 (Fig. 3a, Supplementary Fig. 3a). RESULTS | |
| 42 47 helix structure_element The 8-azanebularine is flipped out of the helix and bound into the active site as its covalent hydrate where it interacts with several amino acids including V351, T375, K376, E396 and R455 (Fig. 3a, Supplementary Fig. 3a). RESULTS | |
| 52 62 bound into protein_state The 8-azanebularine is flipped out of the helix and bound into the active site as its covalent hydrate where it interacts with several amino acids including V351, T375, K376, E396 and R455 (Fig. 3a, Supplementary Fig. 3a). RESULTS | |
| 67 78 active site site The 8-azanebularine is flipped out of the helix and bound into the active site as its covalent hydrate where it interacts with several amino acids including V351, T375, K376, E396 and R455 (Fig. 3a, Supplementary Fig. 3a). RESULTS | |
| 157 161 V351 residue_name_number The 8-azanebularine is flipped out of the helix and bound into the active site as its covalent hydrate where it interacts with several amino acids including V351, T375, K376, E396 and R455 (Fig. 3a, Supplementary Fig. 3a). RESULTS | |
| 163 167 T375 residue_name_number The 8-azanebularine is flipped out of the helix and bound into the active site as its covalent hydrate where it interacts with several amino acids including V351, T375, K376, E396 and R455 (Fig. 3a, Supplementary Fig. 3a). RESULTS | |
| 169 173 K376 residue_name_number The 8-azanebularine is flipped out of the helix and bound into the active site as its covalent hydrate where it interacts with several amino acids including V351, T375, K376, E396 and R455 (Fig. 3a, Supplementary Fig. 3a). RESULTS | |
| 175 179 E396 residue_name_number The 8-azanebularine is flipped out of the helix and bound into the active site as its covalent hydrate where it interacts with several amino acids including V351, T375, K376, E396 and R455 (Fig. 3a, Supplementary Fig. 3a). RESULTS | |
| 184 188 R455 residue_name_number The 8-azanebularine is flipped out of the helix and bound into the active site as its covalent hydrate where it interacts with several amino acids including V351, T375, K376, E396 and R455 (Fig. 3a, Supplementary Fig. 3a). RESULTS | |
| 18 22 E396 residue_name_number The side chain of E396 H-bonds to purine N1 and O6. RESULTS | |
| 23 30 H-bonds bond_interaction The side chain of E396 H-bonds to purine N1 and O6. RESULTS | |
| 34 40 purine chemical The side chain of E396 H-bonds to purine N1 and O6. RESULTS | |
| 57 61 E396 residue_name_number This interaction was expected given the proposed role of E396 in mediating proton transfers to and from N1 of the substrate adenosine. RESULTS | |
| 124 133 adenosine residue_name This interaction was expected given the proposed role of E396 in mediating proton transfers to and from N1 of the substrate adenosine. RESULTS | |
| 19 34 8-azanebularine chemical The 2’-hydroxyl of 8-azanebularine H-bonds to the backbone carbonyl of T375 while the T375 side chain contacts its 3’-phosphodiester. RESULTS | |
| 35 42 H-bonds bond_interaction The 2’-hydroxyl of 8-azanebularine H-bonds to the backbone carbonyl of T375 while the T375 side chain contacts its 3’-phosphodiester. RESULTS | |
| 71 75 T375 residue_name_number The 2’-hydroxyl of 8-azanebularine H-bonds to the backbone carbonyl of T375 while the T375 side chain contacts its 3’-phosphodiester. RESULTS | |
| 86 90 T375 residue_name_number The 2’-hydroxyl of 8-azanebularine H-bonds to the backbone carbonyl of T375 while the T375 side chain contacts its 3’-phosphodiester. RESULTS | |
| 0 4 R455 residue_name_number R455 and K376 help position the flipped nucleotide in the active site by fastening the phosphate backbone flanking the editing site. RESULTS | |
| 9 13 K376 residue_name_number R455 and K376 help position the flipped nucleotide in the active site by fastening the phosphate backbone flanking the editing site. RESULTS | |
| 32 39 flipped protein_state R455 and K376 help position the flipped nucleotide in the active site by fastening the phosphate backbone flanking the editing site. RESULTS | |
| 40 50 nucleotide chemical R455 and K376 help position the flipped nucleotide in the active site by fastening the phosphate backbone flanking the editing site. RESULTS | |
| 58 69 active site site R455 and K376 help position the flipped nucleotide in the active site by fastening the phosphate backbone flanking the editing site. RESULTS | |
| 119 131 editing site site R455 and K376 help position the flipped nucleotide in the active site by fastening the phosphate backbone flanking the editing site. RESULTS | |
| 4 8 R455 residue_name_number The R455 side chain ion pairs with the 5’-phosphodiester of 8-azanebularine while the K376 side chain contacts its 3’-phosphodiester. RESULTS | |
| 20 29 ion pairs bond_interaction The R455 side chain ion pairs with the 5’-phosphodiester of 8-azanebularine while the K376 side chain contacts its 3’-phosphodiester. RESULTS | |
| 60 75 8-azanebularine chemical The R455 side chain ion pairs with the 5’-phosphodiester of 8-azanebularine while the K376 side chain contacts its 3’-phosphodiester. RESULTS | |
| 86 90 K376 residue_name_number The R455 side chain ion pairs with the 5’-phosphodiester of 8-azanebularine while the K376 side chain contacts its 3’-phosphodiester. RESULTS | |
| 26 30 V351 residue_name_number Lastly, the side chain of V351 provides a hydrophobic surface for interaction with the nucleobase of the edited nucleotide. RESULTS | |
| 42 61 hydrophobic surface site Lastly, the side chain of V351 provides a hydrophobic surface for interaction with the nucleobase of the edited nucleotide. RESULTS | |
| 105 111 edited protein_state Lastly, the side chain of V351 provides a hydrophobic surface for interaction with the nucleobase of the edited nucleotide. RESULTS | |
| 112 122 nucleotide chemical Lastly, the side chain of V351 provides a hydrophobic surface for interaction with the nucleobase of the edited nucleotide. RESULTS | |
| 0 3 RNA chemical RNA binding does not alter IHP binding or the H-bonding network linking IHP to the active site. RESULTS | |
| 27 30 IHP chemical RNA binding does not alter IHP binding or the H-bonding network linking IHP to the active site. RESULTS | |
| 46 63 H-bonding network site RNA binding does not alter IHP binding or the H-bonding network linking IHP to the active site. RESULTS | |
| 72 75 IHP chemical RNA binding does not alter IHP binding or the H-bonding network linking IHP to the active site. RESULTS | |
| 83 94 active site site RNA binding does not alter IHP binding or the H-bonding network linking IHP to the active site. RESULTS | |
| 0 5 ADARs protein_type ADARs use a unique mechanism to modify duplex RNA RESULTS | |
| 39 49 duplex RNA structure_element ADARs use a unique mechanism to modify duplex RNA RESULTS | |
| 4 9 ADAR2 protein The ADAR2 base-flipping loop, bearing residue 488, approaches the RNA duplex from the minor groove side at the editing site. RESULTS | |
| 10 28 base-flipping loop structure_element The ADAR2 base-flipping loop, bearing residue 488, approaches the RNA duplex from the minor groove side at the editing site. RESULTS | |
| 46 49 488 residue_number The ADAR2 base-flipping loop, bearing residue 488, approaches the RNA duplex from the minor groove side at the editing site. RESULTS | |
| 66 76 RNA duplex structure_element The ADAR2 base-flipping loop, bearing residue 488, approaches the RNA duplex from the minor groove side at the editing site. RESULTS | |
| 86 98 minor groove site The ADAR2 base-flipping loop, bearing residue 488, approaches the RNA duplex from the minor groove side at the editing site. RESULTS | |
| 111 123 editing site site The ADAR2 base-flipping loop, bearing residue 488, approaches the RNA duplex from the minor groove side at the editing site. RESULTS | |
| 98 109 flipped out protein_state The side chain of this amino acid penetrates the helix where it occupies the space vacated by the flipped out base and H-bonds to the complementary strand orphaned base and to the 2’ hydroxyl of the nucleotide immediately 5’ to the editing site (Figs. 3b, 3c). RESULTS | |
| 110 114 base chemical The side chain of this amino acid penetrates the helix where it occupies the space vacated by the flipped out base and H-bonds to the complementary strand orphaned base and to the 2’ hydroxyl of the nucleotide immediately 5’ to the editing site (Figs. 3b, 3c). RESULTS | |
| 119 126 H-bonds bond_interaction The side chain of this amino acid penetrates the helix where it occupies the space vacated by the flipped out base and H-bonds to the complementary strand orphaned base and to the 2’ hydroxyl of the nucleotide immediately 5’ to the editing site (Figs. 3b, 3c). RESULTS | |
| 155 163 orphaned protein_state The side chain of this amino acid penetrates the helix where it occupies the space vacated by the flipped out base and H-bonds to the complementary strand orphaned base and to the 2’ hydroxyl of the nucleotide immediately 5’ to the editing site (Figs. 3b, 3c). RESULTS | |
| 164 168 base chemical The side chain of this amino acid penetrates the helix where it occupies the space vacated by the flipped out base and H-bonds to the complementary strand orphaned base and to the 2’ hydroxyl of the nucleotide immediately 5’ to the editing site (Figs. 3b, 3c). RESULTS | |
| 232 244 editing site site The side chain of this amino acid penetrates the helix where it occupies the space vacated by the flipped out base and H-bonds to the complementary strand orphaned base and to the 2’ hydroxyl of the nucleotide immediately 5’ to the editing site (Figs. 3b, 3c). RESULTS | |
| 12 22 structures evidence In the four structures reported here, three different combinations of helix-penetrating residue and orphan base are observed (i.e. E488 + U, E488 + C and Q488 + C) and all three combinations show the same side chain and base positions (Figs. 3b, 3c, Supplementary Fig. 4a for overlay of all three). RESULTS | |
| 100 106 orphan protein_state In the four structures reported here, three different combinations of helix-penetrating residue and orphan base are observed (i.e. E488 + U, E488 + C and Q488 + C) and all three combinations show the same side chain and base positions (Figs. 3b, 3c, Supplementary Fig. 4a for overlay of all three). RESULTS | |
| 107 111 base chemical In the four structures reported here, three different combinations of helix-penetrating residue and orphan base are observed (i.e. E488 + U, E488 + C and Q488 + C) and all three combinations show the same side chain and base positions (Figs. 3b, 3c, Supplementary Fig. 4a for overlay of all three). RESULTS | |
| 131 135 E488 residue_name_number In the four structures reported here, three different combinations of helix-penetrating residue and orphan base are observed (i.e. E488 + U, E488 + C and Q488 + C) and all three combinations show the same side chain and base positions (Figs. 3b, 3c, Supplementary Fig. 4a for overlay of all three). RESULTS | |
| 138 139 U residue_name In the four structures reported here, three different combinations of helix-penetrating residue and orphan base are observed (i.e. E488 + U, E488 + C and Q488 + C) and all three combinations show the same side chain and base positions (Figs. 3b, 3c, Supplementary Fig. 4a for overlay of all three). RESULTS | |
| 141 145 E488 residue_name_number In the four structures reported here, three different combinations of helix-penetrating residue and orphan base are observed (i.e. E488 + U, E488 + C and Q488 + C) and all three combinations show the same side chain and base positions (Figs. 3b, 3c, Supplementary Fig. 4a for overlay of all three). RESULTS | |
| 148 149 C residue_name In the four structures reported here, three different combinations of helix-penetrating residue and orphan base are observed (i.e. E488 + U, E488 + C and Q488 + C) and all three combinations show the same side chain and base positions (Figs. 3b, 3c, Supplementary Fig. 4a for overlay of all three). RESULTS | |
| 154 158 Q488 residue_name_number In the four structures reported here, three different combinations of helix-penetrating residue and orphan base are observed (i.e. E488 + U, E488 + C and Q488 + C) and all three combinations show the same side chain and base positions (Figs. 3b, 3c, Supplementary Fig. 4a for overlay of all three). RESULTS | |
| 161 162 C residue_name In the four structures reported here, three different combinations of helix-penetrating residue and orphan base are observed (i.e. E488 + U, E488 + C and Q488 + C) and all three combinations show the same side chain and base positions (Figs. 3b, 3c, Supplementary Fig. 4a for overlay of all three). RESULTS | |
| 276 283 overlay experimental_method In the four structures reported here, three different combinations of helix-penetrating residue and orphan base are observed (i.e. E488 + U, E488 + C and Q488 + C) and all three combinations show the same side chain and base positions (Figs. 3b, 3c, Supplementary Fig. 4a for overlay of all three). RESULTS | |
| 21 33 complex with protein_state For instance, in the complex with hADAR2d E488Q and the Bdf2-C duplex, the protein recognizes an orphaned C by donating H-bonds from Nε2 to cytosine N3 and from its backbone NH to cytosine O2 (Fig. 3b). RESULTS | |
| 34 41 hADAR2d mutant For instance, in the complex with hADAR2d E488Q and the Bdf2-C duplex, the protein recognizes an orphaned C by donating H-bonds from Nε2 to cytosine N3 and from its backbone NH to cytosine O2 (Fig. 3b). RESULTS | |
| 42 47 E488Q mutant For instance, in the complex with hADAR2d E488Q and the Bdf2-C duplex, the protein recognizes an orphaned C by donating H-bonds from Nε2 to cytosine N3 and from its backbone NH to cytosine O2 (Fig. 3b). RESULTS | |
| 56 69 Bdf2-C duplex chemical For instance, in the complex with hADAR2d E488Q and the Bdf2-C duplex, the protein recognizes an orphaned C by donating H-bonds from Nε2 to cytosine N3 and from its backbone NH to cytosine O2 (Fig. 3b). RESULTS | |
| 97 105 orphaned protein_state For instance, in the complex with hADAR2d E488Q and the Bdf2-C duplex, the protein recognizes an orphaned C by donating H-bonds from Nε2 to cytosine N3 and from its backbone NH to cytosine O2 (Fig. 3b). RESULTS | |
| 106 107 C residue_name For instance, in the complex with hADAR2d E488Q and the Bdf2-C duplex, the protein recognizes an orphaned C by donating H-bonds from Nε2 to cytosine N3 and from its backbone NH to cytosine O2 (Fig. 3b). RESULTS | |
| 120 127 H-bonds bond_interaction For instance, in the complex with hADAR2d E488Q and the Bdf2-C duplex, the protein recognizes an orphaned C by donating H-bonds from Nε2 to cytosine N3 and from its backbone NH to cytosine O2 (Fig. 3b). RESULTS | |
| 140 148 cytosine residue_name For instance, in the complex with hADAR2d E488Q and the Bdf2-C duplex, the protein recognizes an orphaned C by donating H-bonds from Nε2 to cytosine N3 and from its backbone NH to cytosine O2 (Fig. 3b). RESULTS | |
| 180 188 cytosine residue_name For instance, in the complex with hADAR2d E488Q and the Bdf2-C duplex, the protein recognizes an orphaned C by donating H-bonds from Nε2 to cytosine N3 and from its backbone NH to cytosine O2 (Fig. 3b). RESULTS | |
| 7 19 complex with protein_state In the complex with hADAR2d WT and the Bdf2-U duplex, a similar interaction is observed with the E488 backbone NH hydrogen bonded to the uracil O2 and the E488 side chain H-bonded to the uracil N3H (Fig. 3c). RESULTS | |
| 20 27 hADAR2d mutant In the complex with hADAR2d WT and the Bdf2-U duplex, a similar interaction is observed with the E488 backbone NH hydrogen bonded to the uracil O2 and the E488 side chain H-bonded to the uracil N3H (Fig. 3c). RESULTS | |
| 28 30 WT protein_state In the complex with hADAR2d WT and the Bdf2-U duplex, a similar interaction is observed with the E488 backbone NH hydrogen bonded to the uracil O2 and the E488 side chain H-bonded to the uracil N3H (Fig. 3c). RESULTS | |
| 39 52 Bdf2-U duplex chemical In the complex with hADAR2d WT and the Bdf2-U duplex, a similar interaction is observed with the E488 backbone NH hydrogen bonded to the uracil O2 and the E488 side chain H-bonded to the uracil N3H (Fig. 3c). RESULTS | |
| 97 101 E488 residue_name_number In the complex with hADAR2d WT and the Bdf2-U duplex, a similar interaction is observed with the E488 backbone NH hydrogen bonded to the uracil O2 and the E488 side chain H-bonded to the uracil N3H (Fig. 3c). RESULTS | |
| 114 129 hydrogen bonded bond_interaction In the complex with hADAR2d WT and the Bdf2-U duplex, a similar interaction is observed with the E488 backbone NH hydrogen bonded to the uracil O2 and the E488 side chain H-bonded to the uracil N3H (Fig. 3c). RESULTS | |
| 137 143 uracil residue_name In the complex with hADAR2d WT and the Bdf2-U duplex, a similar interaction is observed with the E488 backbone NH hydrogen bonded to the uracil O2 and the E488 side chain H-bonded to the uracil N3H (Fig. 3c). RESULTS | |
| 155 159 E488 residue_name_number In the complex with hADAR2d WT and the Bdf2-U duplex, a similar interaction is observed with the E488 backbone NH hydrogen bonded to the uracil O2 and the E488 side chain H-bonded to the uracil N3H (Fig. 3c). RESULTS | |
| 171 179 H-bonded bond_interaction In the complex with hADAR2d WT and the Bdf2-U duplex, a similar interaction is observed with the E488 backbone NH hydrogen bonded to the uracil O2 and the E488 side chain H-bonded to the uracil N3H (Fig. 3c). RESULTS | |
| 187 193 uracil residue_name In the complex with hADAR2d WT and the Bdf2-U duplex, a similar interaction is observed with the E488 backbone NH hydrogen bonded to the uracil O2 and the E488 side chain H-bonded to the uracil N3H (Fig. 3c). RESULTS | |
| 19 24 E488Q mutant Interestingly, the E488Q mutant was discovered in a screen for highly active ADAR2 mutants and this residue was suggested to be involved in base flipping given its effect on editing substrates with a fluorescent nucleobase at the editing site. RESULTS | |
| 25 31 mutant protein_state Interestingly, the E488Q mutant was discovered in a screen for highly active ADAR2 mutants and this residue was suggested to be involved in base flipping given its effect on editing substrates with a fluorescent nucleobase at the editing site. RESULTS | |
| 63 76 highly active protein_state Interestingly, the E488Q mutant was discovered in a screen for highly active ADAR2 mutants and this residue was suggested to be involved in base flipping given its effect on editing substrates with a fluorescent nucleobase at the editing site. RESULTS | |
| 77 82 ADAR2 protein Interestingly, the E488Q mutant was discovered in a screen for highly active ADAR2 mutants and this residue was suggested to be involved in base flipping given its effect on editing substrates with a fluorescent nucleobase at the editing site. RESULTS | |
| 83 90 mutants protein_state Interestingly, the E488Q mutant was discovered in a screen for highly active ADAR2 mutants and this residue was suggested to be involved in base flipping given its effect on editing substrates with a fluorescent nucleobase at the editing site. RESULTS | |
| 230 242 editing site site Interestingly, the E488Q mutant was discovered in a screen for highly active ADAR2 mutants and this residue was suggested to be involved in base flipping given its effect on editing substrates with a fluorescent nucleobase at the editing site. RESULTS | |
| 0 5 ADARs protein_type ADARs react preferentially with adenosines in A•C mismatches and A-U pairs over A•A and A•G mismatches. RESULTS | |
| 32 42 adenosines residue_name ADARs react preferentially with adenosines in A•C mismatches and A-U pairs over A•A and A•G mismatches. RESULTS | |
| 46 49 A•C structure_element ADARs react preferentially with adenosines in A•C mismatches and A-U pairs over A•A and A•G mismatches. RESULTS | |
| 65 74 A-U pairs structure_element ADARs react preferentially with adenosines in A•C mismatches and A-U pairs over A•A and A•G mismatches. RESULTS | |
| 80 83 A•A structure_element ADARs react preferentially with adenosines in A•C mismatches and A-U pairs over A•A and A•G mismatches. RESULTS | |
| 88 91 A•G structure_element ADARs react preferentially with adenosines in A•C mismatches and A-U pairs over A•A and A•G mismatches. RESULTS | |
| 2 8 purine chemical A purine at the orphan base position (in its anti conformation) would clash with the 488 residue explaining the preference for pyrimidines here. RESULTS | |
| 16 22 orphan protein_state A purine at the orphan base position (in its anti conformation) would clash with the 488 residue explaining the preference for pyrimidines here. RESULTS | |
| 23 27 base chemical A purine at the orphan base position (in its anti conformation) would clash with the 488 residue explaining the preference for pyrimidines here. RESULTS | |
| 85 88 488 residue_number A purine at the orphan base position (in its anti conformation) would clash with the 488 residue explaining the preference for pyrimidines here. RESULTS | |
| 127 138 pyrimidines chemical A purine at the orphan base position (in its anti conformation) would clash with the 488 residue explaining the preference for pyrimidines here. RESULTS | |
| 23 26 488 residue_number The interaction of the 488 residue with the orphaned base is reminiscent of an interaction observed for Hha I DNA methyltransfersase (MTase), a duplex DNA modifying enzyme that also uses a base flipping mechanism to access 2’-deoxycytidine (dC) for methylation. RESULTS | |
| 44 52 orphaned protein_state The interaction of the 488 residue with the orphaned base is reminiscent of an interaction observed for Hha I DNA methyltransfersase (MTase), a duplex DNA modifying enzyme that also uses a base flipping mechanism to access 2’-deoxycytidine (dC) for methylation. RESULTS | |
| 53 57 base chemical The interaction of the 488 residue with the orphaned base is reminiscent of an interaction observed for Hha I DNA methyltransfersase (MTase), a duplex DNA modifying enzyme that also uses a base flipping mechanism to access 2’-deoxycytidine (dC) for methylation. RESULTS | |
| 104 132 Hha I DNA methyltransfersase protein_type The interaction of the 488 residue with the orphaned base is reminiscent of an interaction observed for Hha I DNA methyltransfersase (MTase), a duplex DNA modifying enzyme that also uses a base flipping mechanism to access 2’-deoxycytidine (dC) for methylation. RESULTS | |
| 134 139 MTase protein_type The interaction of the 488 residue with the orphaned base is reminiscent of an interaction observed for Hha I DNA methyltransfersase (MTase), a duplex DNA modifying enzyme that also uses a base flipping mechanism to access 2’-deoxycytidine (dC) for methylation. RESULTS | |
| 144 154 duplex DNA structure_element The interaction of the 488 residue with the orphaned base is reminiscent of an interaction observed for Hha I DNA methyltransfersase (MTase), a duplex DNA modifying enzyme that also uses a base flipping mechanism to access 2’-deoxycytidine (dC) for methylation. RESULTS | |
| 223 239 2’-deoxycytidine residue_name The interaction of the 488 residue with the orphaned base is reminiscent of an interaction observed for Hha I DNA methyltransfersase (MTase), a duplex DNA modifying enzyme that also uses a base flipping mechanism to access 2’-deoxycytidine (dC) for methylation. RESULTS | |
| 241 243 dC residue_name The interaction of the 488 residue with the orphaned base is reminiscent of an interaction observed for Hha I DNA methyltransfersase (MTase), a duplex DNA modifying enzyme that also uses a base flipping mechanism to access 2’-deoxycytidine (dC) for methylation. RESULTS | |
| 17 21 Q237 residue_name_number For that enzyme, Q237 H-bonds to an orphaned dG while it fills the void left by the flipped out dC (Supplementary Fig. 4b). RESULTS | |
| 22 29 H-bonds bond_interaction For that enzyme, Q237 H-bonds to an orphaned dG while it fills the void left by the flipped out dC (Supplementary Fig. 4b). RESULTS | |
| 36 44 orphaned protein_state For that enzyme, Q237 H-bonds to an orphaned dG while it fills the void left by the flipped out dC (Supplementary Fig. 4b). RESULTS | |
| 45 47 dG residue_name For that enzyme, Q237 H-bonds to an orphaned dG while it fills the void left by the flipped out dC (Supplementary Fig. 4b). RESULTS | |
| 84 95 flipped out protein_state For that enzyme, Q237 H-bonds to an orphaned dG while it fills the void left by the flipped out dC (Supplementary Fig. 4b). RESULTS | |
| 96 98 dC residue_name For that enzyme, Q237 H-bonds to an orphaned dG while it fills the void left by the flipped out dC (Supplementary Fig. 4b). RESULTS | |
| 17 24 glycine residue_name In addition, two glycine residues flank Q237 allowing the loop to adopt the conformation necessary for penetration into the helix. RESULTS | |
| 40 44 Q237 residue_name_number In addition, two glycine residues flank Q237 allowing the loop to adopt the conformation necessary for penetration into the helix. RESULTS | |
| 58 62 loop structure_element In addition, two glycine residues flank Q237 allowing the loop to adopt the conformation necessary for penetration into the helix. RESULTS | |
| 124 129 helix structure_element In addition, two glycine residues flank Q237 allowing the loop to adopt the conformation necessary for penetration into the helix. RESULTS | |
| 4 17 flipping loop structure_element The flipping loop in ADAR2 (i.e. aa487–489) also has the helix-penetrating residue flanked by glycines. RESULTS | |
| 21 26 ADAR2 protein The flipping loop in ADAR2 (i.e. aa487–489) also has the helix-penetrating residue flanked by glycines. RESULTS | |
| 35 42 487–489 residue_range The flipping loop in ADAR2 (i.e. aa487–489) also has the helix-penetrating residue flanked by glycines. RESULTS | |
| 94 102 glycines residue_name The flipping loop in ADAR2 (i.e. aa487–489) also has the helix-penetrating residue flanked by glycines. RESULTS | |
| 32 41 DNA MTase protein_type However, unlike the case of the DNA MTase that approaches the DNA from the major groove, the ADAR2 loop approaches the duplex from the minor groove side. RESULTS | |
| 62 65 DNA chemical However, unlike the case of the DNA MTase that approaches the DNA from the major groove, the ADAR2 loop approaches the duplex from the minor groove side. RESULTS | |
| 75 87 major groove site However, unlike the case of the DNA MTase that approaches the DNA from the major groove, the ADAR2 loop approaches the duplex from the minor groove side. RESULTS | |
| 93 98 ADAR2 protein However, unlike the case of the DNA MTase that approaches the DNA from the major groove, the ADAR2 loop approaches the duplex from the minor groove side. RESULTS | |
| 99 103 loop structure_element However, unlike the case of the DNA MTase that approaches the DNA from the major groove, the ADAR2 loop approaches the duplex from the minor groove side. RESULTS | |
| 119 125 duplex structure_element However, unlike the case of the DNA MTase that approaches the DNA from the major groove, the ADAR2 loop approaches the duplex from the minor groove side. RESULTS | |
| 135 147 minor groove site However, unlike the case of the DNA MTase that approaches the DNA from the major groove, the ADAR2 loop approaches the duplex from the minor groove side. RESULTS | |
| 52 73 intercalating residue site Such an approach requires deeper penetration of the intercalating residue to access the H-bonding sites on the orphaned base, necessitating an additional conformational change in the RNA duplex. RESULTS | |
| 88 103 H-bonding sites site Such an approach requires deeper penetration of the intercalating residue to access the H-bonding sites on the orphaned base, necessitating an additional conformational change in the RNA duplex. RESULTS | |
| 111 119 orphaned protein_state Such an approach requires deeper penetration of the intercalating residue to access the H-bonding sites on the orphaned base, necessitating an additional conformational change in the RNA duplex. RESULTS | |
| 120 124 base chemical Such an approach requires deeper penetration of the intercalating residue to access the H-bonding sites on the orphaned base, necessitating an additional conformational change in the RNA duplex. RESULTS | |
| 183 193 RNA duplex structure_element Such an approach requires deeper penetration of the intercalating residue to access the H-bonding sites on the orphaned base, necessitating an additional conformational change in the RNA duplex. RESULTS | |
| 70 82 editing site site This change includes shifting of the base pairs immediately 5’ to the editing site toward the helical axis and a widening of the major groove opposite the editing site (Figs. 4a, 4b, Supplementary Video 1). RESULTS | |
| 129 141 major groove site This change includes shifting of the base pairs immediately 5’ to the editing site toward the helical axis and a widening of the major groove opposite the editing site (Figs. 4a, 4b, Supplementary Video 1). RESULTS | |
| 155 167 editing site site This change includes shifting of the base pairs immediately 5’ to the editing site toward the helical axis and a widening of the major groove opposite the editing site (Figs. 4a, 4b, Supplementary Video 1). RESULTS | |
| 19 36 hADAR2d WT–Bdf2-U complex_assembly "In the case of the hADAR2d WT–Bdf2-U RNA, this shift is accompanied by a shearing of the U11-A13' base pair with U11 shifted further in the direction of the major groove creating an unusual U-A ""wobble"" interaction with adenine N6 and N1 within H-bonding distance to uracil N3H and O2, respectively (Fig. 4c, Supplementary Fig. 3b)." RESULTS | |
| 37 40 RNA chemical "In the case of the hADAR2d WT–Bdf2-U RNA, this shift is accompanied by a shearing of the U11-A13' base pair with U11 shifted further in the direction of the major groove creating an unusual U-A ""wobble"" interaction with adenine N6 and N1 within H-bonding distance to uracil N3H and O2, respectively (Fig. 4c, Supplementary Fig. 3b)." RESULTS | |
| 89 92 U11 residue_name_number "In the case of the hADAR2d WT–Bdf2-U RNA, this shift is accompanied by a shearing of the U11-A13' base pair with U11 shifted further in the direction of the major groove creating an unusual U-A ""wobble"" interaction with adenine N6 and N1 within H-bonding distance to uracil N3H and O2, respectively (Fig. 4c, Supplementary Fig. 3b)." RESULTS | |
| 93 96 A13 residue_name_number "In the case of the hADAR2d WT–Bdf2-U RNA, this shift is accompanied by a shearing of the U11-A13' base pair with U11 shifted further in the direction of the major groove creating an unusual U-A ""wobble"" interaction with adenine N6 and N1 within H-bonding distance to uracil N3H and O2, respectively (Fig. 4c, Supplementary Fig. 3b)." RESULTS | |
| 113 116 U11 residue_name_number "In the case of the hADAR2d WT–Bdf2-U RNA, this shift is accompanied by a shearing of the U11-A13' base pair with U11 shifted further in the direction of the major groove creating an unusual U-A ""wobble"" interaction with adenine N6 and N1 within H-bonding distance to uracil N3H and O2, respectively (Fig. 4c, Supplementary Fig. 3b)." RESULTS | |
| 157 169 major groove site "In the case of the hADAR2d WT–Bdf2-U RNA, this shift is accompanied by a shearing of the U11-A13' base pair with U11 shifted further in the direction of the major groove creating an unusual U-A ""wobble"" interaction with adenine N6 and N1 within H-bonding distance to uracil N3H and O2, respectively (Fig. 4c, Supplementary Fig. 3b)." RESULTS | |
| 190 202 "U-A ""wobble""" structure_element "In the case of the hADAR2d WT–Bdf2-U RNA, this shift is accompanied by a shearing of the U11-A13' base pair with U11 shifted further in the direction of the major groove creating an unusual U-A ""wobble"" interaction with adenine N6 and N1 within H-bonding distance to uracil N3H and O2, respectively (Fig. 4c, Supplementary Fig. 3b)." RESULTS | |
| 220 227 adenine residue_name "In the case of the hADAR2d WT–Bdf2-U RNA, this shift is accompanied by a shearing of the U11-A13' base pair with U11 shifted further in the direction of the major groove creating an unusual U-A ""wobble"" interaction with adenine N6 and N1 within H-bonding distance to uracil N3H and O2, respectively (Fig. 4c, Supplementary Fig. 3b)." RESULTS | |
| 245 254 H-bonding bond_interaction "In the case of the hADAR2d WT–Bdf2-U RNA, this shift is accompanied by a shearing of the U11-A13' base pair with U11 shifted further in the direction of the major groove creating an unusual U-A ""wobble"" interaction with adenine N6 and N1 within H-bonding distance to uracil N3H and O2, respectively (Fig. 4c, Supplementary Fig. 3b)." RESULTS | |
| 267 273 uracil residue_name "In the case of the hADAR2d WT–Bdf2-U RNA, this shift is accompanied by a shearing of the U11-A13' base pair with U11 shifted further in the direction of the major groove creating an unusual U-A ""wobble"" interaction with adenine N6 and N1 within H-bonding distance to uracil N3H and O2, respectively (Fig. 4c, Supplementary Fig. 3b)." RESULTS | |
| 92 99 adenine residue_name This type of wobble pair has been observed before and requires either the imino tautomer of adenine or the enol tautomer of uracil. RESULTS | |
| 124 130 uracil residue_name This type of wobble pair has been observed before and requires either the imino tautomer of adenine or the enol tautomer of uracil. RESULTS | |
| 4 8 ADAR protein_type The ADAR-induced distortion in RNA conformation results in a kink in the RNA strand opposite the editing site (Fig. 4b). RESULTS | |
| 31 34 RNA chemical The ADAR-induced distortion in RNA conformation results in a kink in the RNA strand opposite the editing site (Fig. 4b). RESULTS | |
| 61 65 kink structure_element The ADAR-induced distortion in RNA conformation results in a kink in the RNA strand opposite the editing site (Fig. 4b). RESULTS | |
| 73 76 RNA chemical The ADAR-induced distortion in RNA conformation results in a kink in the RNA strand opposite the editing site (Fig. 4b). RESULTS | |
| 97 109 editing site site The ADAR-induced distortion in RNA conformation results in a kink in the RNA strand opposite the editing site (Fig. 4b). RESULTS | |
| 5 9 kink structure_element This kink is stabilized by interactions of the side chains of R510 and S495 with phosphodiesters in the RNA backbone of the unedited strand (Fig. 4a). RESULTS | |
| 62 66 R510 residue_name_number This kink is stabilized by interactions of the side chains of R510 and S495 with phosphodiesters in the RNA backbone of the unedited strand (Fig. 4a). RESULTS | |
| 71 75 S495 residue_name_number This kink is stabilized by interactions of the side chains of R510 and S495 with phosphodiesters in the RNA backbone of the unedited strand (Fig. 4a). RESULTS | |
| 104 107 RNA chemical This kink is stabilized by interactions of the side chains of R510 and S495 with phosphodiesters in the RNA backbone of the unedited strand (Fig. 4a). RESULTS | |
| 15 20 ADAR2 protein Interestingly, ADAR2’s flipping loop approach from the minor groove side is like that seen with certain DNA repair glycosylases (e.g. UDG, HOGG1, and AAG) that also project intercalating residues from loops bound in the minor groove (Supplementary Fig. 5a). RESULTS | |
| 23 36 flipping loop structure_element Interestingly, ADAR2’s flipping loop approach from the minor groove side is like that seen with certain DNA repair glycosylases (e.g. UDG, HOGG1, and AAG) that also project intercalating residues from loops bound in the minor groove (Supplementary Fig. 5a). RESULTS | |
| 55 67 minor groove site Interestingly, ADAR2’s flipping loop approach from the minor groove side is like that seen with certain DNA repair glycosylases (e.g. UDG, HOGG1, and AAG) that also project intercalating residues from loops bound in the minor groove (Supplementary Fig. 5a). RESULTS | |
| 104 127 DNA repair glycosylases protein_type Interestingly, ADAR2’s flipping loop approach from the minor groove side is like that seen with certain DNA repair glycosylases (e.g. UDG, HOGG1, and AAG) that also project intercalating residues from loops bound in the minor groove (Supplementary Fig. 5a). RESULTS | |
| 134 137 UDG protein Interestingly, ADAR2’s flipping loop approach from the minor groove side is like that seen with certain DNA repair glycosylases (e.g. UDG, HOGG1, and AAG) that also project intercalating residues from loops bound in the minor groove (Supplementary Fig. 5a). RESULTS | |
| 139 144 HOGG1 protein Interestingly, ADAR2’s flipping loop approach from the minor groove side is like that seen with certain DNA repair glycosylases (e.g. UDG, HOGG1, and AAG) that also project intercalating residues from loops bound in the minor groove (Supplementary Fig. 5a). RESULTS | |
| 150 153 AAG protein Interestingly, ADAR2’s flipping loop approach from the minor groove side is like that seen with certain DNA repair glycosylases (e.g. UDG, HOGG1, and AAG) that also project intercalating residues from loops bound in the minor groove (Supplementary Fig. 5a). RESULTS | |
| 201 206 loops structure_element Interestingly, ADAR2’s flipping loop approach from the minor groove side is like that seen with certain DNA repair glycosylases (e.g. UDG, HOGG1, and AAG) that also project intercalating residues from loops bound in the minor groove (Supplementary Fig. 5a). RESULTS | |
| 207 215 bound in protein_state Interestingly, ADAR2’s flipping loop approach from the minor groove side is like that seen with certain DNA repair glycosylases (e.g. UDG, HOGG1, and AAG) that also project intercalating residues from loops bound in the minor groove (Supplementary Fig. 5a). RESULTS | |
| 220 232 minor groove site Interestingly, ADAR2’s flipping loop approach from the minor groove side is like that seen with certain DNA repair glycosylases (e.g. UDG, HOGG1, and AAG) that also project intercalating residues from loops bound in the minor groove (Supplementary Fig. 5a). RESULTS | |
| 42 52 DNA duplex chemical However, these enzymes typically bend the DNA duplex at the site of modification to allow for penetration of intercalating residues and damage recognition. RESULTS | |
| 6 13 hADAR2d mutant While hADAR2d clearly alters the duplex conformation to gain access to the modification site from the minor groove, it does not bend the RNA duplex (Figs. 2a, 2b, 4b). RESULTS | |
| 102 114 minor groove site While hADAR2d clearly alters the duplex conformation to gain access to the modification site from the minor groove, it does not bend the RNA duplex (Figs. 2a, 2b, 4b). RESULTS | |
| 137 147 RNA duplex structure_element While hADAR2d clearly alters the duplex conformation to gain access to the modification site from the minor groove, it does not bend the RNA duplex (Figs. 2a, 2b, 4b). RESULTS | |
| 13 18 ADARs protein_type Furthermore, ADARs do not modify duplex DNA. RESULTS | |
| 33 43 duplex DNA structure_element Furthermore, ADARs do not modify duplex DNA. RESULTS | |
| 4 7 DNA chemical The DNA B-form helix has groove widths and depths that would prevent productive interactions with ADAR. RESULTS | |
| 8 20 B-form helix structure_element The DNA B-form helix has groove widths and depths that would prevent productive interactions with ADAR. RESULTS | |
| 98 102 ADAR protein_type The DNA B-form helix has groove widths and depths that would prevent productive interactions with ADAR. RESULTS | |
| 14 18 ADAR protein_type For instance, ADAR can readily penetrate an A-form helix from the minor groove side and place the helix-penetrating residue in the space occupied by the editing site base (Supplementary Fig. 6). RESULTS | |
| 44 56 A-form helix structure_element For instance, ADAR can readily penetrate an A-form helix from the minor groove side and place the helix-penetrating residue in the space occupied by the editing site base (Supplementary Fig. 6). RESULTS | |
| 66 78 minor groove site For instance, ADAR can readily penetrate an A-form helix from the minor groove side and place the helix-penetrating residue in the space occupied by the editing site base (Supplementary Fig. 6). RESULTS | |
| 153 165 editing site site For instance, ADAR can readily penetrate an A-form helix from the minor groove side and place the helix-penetrating residue in the space occupied by the editing site base (Supplementary Fig. 6). RESULTS | |
| 43 55 minor groove site However, this residue cannot penetrate the minor groove enough to occupy the base position in a B-form helix (Supplementary Fig. 6). RESULTS | |
| 96 108 B-form helix structure_element However, this residue cannot penetrate the minor groove enough to occupy the base position in a B-form helix (Supplementary Fig. 6). RESULTS | |
| 13 16 DNA chemical Furthermore, DNA lacks the 2’ hydroxyls that are used by ADAR for substrate recognition (Fig. 2c). RESULTS | |
| 57 61 ADAR protein_type Furthermore, DNA lacks the 2’ hydroxyls that are used by ADAR for substrate recognition (Fig. 2c). RESULTS | |
| 6 13 hADAR2d mutant Thus, hADAR2d uses a substrate recognition and base flipping mechanism with similarities to other known nucleic acid-modifying enzymes but uniquely suited for reaction with adenosine in the context of duplex RNA. RESULTS | |
| 104 134 nucleic acid-modifying enzymes protein_type Thus, hADAR2d uses a substrate recognition and base flipping mechanism with similarities to other known nucleic acid-modifying enzymes but uniquely suited for reaction with adenosine in the context of duplex RNA. RESULTS | |
| 173 182 adenosine residue_name Thus, hADAR2d uses a substrate recognition and base flipping mechanism with similarities to other known nucleic acid-modifying enzymes but uniquely suited for reaction with adenosine in the context of duplex RNA. RESULTS | |
| 201 211 duplex RNA structure_element Thus, hADAR2d uses a substrate recognition and base flipping mechanism with similarities to other known nucleic acid-modifying enzymes but uniquely suited for reaction with adenosine in the context of duplex RNA. RESULTS | |
| 0 10 Structures evidence Structures explain nearest neighbor preferences RESULTS | |
| 0 5 ADARs protein_type ADARs have a preference for editing adenosines with 5’ nearest neighbor U (or A) and 3’ nearest neighbor G. The ADAR2 flipping loop occupies the minor groove spanning the three base pairs that include the nearest neighbor nucleotides flanking the edited base (Figs. 3b, 3c). RESULTS | |
| 36 46 adenosines residue_name ADARs have a preference for editing adenosines with 5’ nearest neighbor U (or A) and 3’ nearest neighbor G. The ADAR2 flipping loop occupies the minor groove spanning the three base pairs that include the nearest neighbor nucleotides flanking the edited base (Figs. 3b, 3c). RESULTS | |
| 72 73 U residue_name ADARs have a preference for editing adenosines with 5’ nearest neighbor U (or A) and 3’ nearest neighbor G. The ADAR2 flipping loop occupies the minor groove spanning the three base pairs that include the nearest neighbor nucleotides flanking the edited base (Figs. 3b, 3c). RESULTS | |
| 78 79 A residue_name ADARs have a preference for editing adenosines with 5’ nearest neighbor U (or A) and 3’ nearest neighbor G. The ADAR2 flipping loop occupies the minor groove spanning the three base pairs that include the nearest neighbor nucleotides flanking the edited base (Figs. 3b, 3c). RESULTS | |
| 105 106 G residue_name ADARs have a preference for editing adenosines with 5’ nearest neighbor U (or A) and 3’ nearest neighbor G. The ADAR2 flipping loop occupies the minor groove spanning the three base pairs that include the nearest neighbor nucleotides flanking the edited base (Figs. 3b, 3c). RESULTS | |
| 112 117 ADAR2 protein ADARs have a preference for editing adenosines with 5’ nearest neighbor U (or A) and 3’ nearest neighbor G. The ADAR2 flipping loop occupies the minor groove spanning the three base pairs that include the nearest neighbor nucleotides flanking the edited base (Figs. 3b, 3c). RESULTS | |
| 118 131 flipping loop structure_element ADARs have a preference for editing adenosines with 5’ nearest neighbor U (or A) and 3’ nearest neighbor G. The ADAR2 flipping loop occupies the minor groove spanning the three base pairs that include the nearest neighbor nucleotides flanking the edited base (Figs. 3b, 3c). RESULTS | |
| 145 157 minor groove site ADARs have a preference for editing adenosines with 5’ nearest neighbor U (or A) and 3’ nearest neighbor G. The ADAR2 flipping loop occupies the minor groove spanning the three base pairs that include the nearest neighbor nucleotides flanking the edited base (Figs. 3b, 3c). RESULTS | |
| 68 69 U residue_name As described above, the base pair including the 5’ nearest neighbor U (U11-A13’ in the Bdf2 duplex) is shifted from the position it would occupy in a typical A-form helix to accommodate the loop (Fig. 4a). RESULTS | |
| 71 74 U11 residue_name_number As described above, the base pair including the 5’ nearest neighbor U (U11-A13’ in the Bdf2 duplex) is shifted from the position it would occupy in a typical A-form helix to accommodate the loop (Fig. 4a). RESULTS | |
| 75 78 A13 residue_name_number As described above, the base pair including the 5’ nearest neighbor U (U11-A13’ in the Bdf2 duplex) is shifted from the position it would occupy in a typical A-form helix to accommodate the loop (Fig. 4a). RESULTS | |
| 87 91 Bdf2 chemical As described above, the base pair including the 5’ nearest neighbor U (U11-A13’ in the Bdf2 duplex) is shifted from the position it would occupy in a typical A-form helix to accommodate the loop (Fig. 4a). RESULTS | |
| 158 170 A-form helix structure_element As described above, the base pair including the 5’ nearest neighbor U (U11-A13’ in the Bdf2 duplex) is shifted from the position it would occupy in a typical A-form helix to accommodate the loop (Fig. 4a). RESULTS | |
| 190 194 loop structure_element As described above, the base pair including the 5’ nearest neighbor U (U11-A13’ in the Bdf2 duplex) is shifted from the position it would occupy in a typical A-form helix to accommodate the loop (Fig. 4a). RESULTS | |
| 10 22 minor groove site Also, the minor groove edge of this pair is juxtaposed to the protein backbone at G489. RESULTS | |
| 82 86 G489 residue_name_number Also, the minor groove edge of this pair is juxtaposed to the protein backbone at G489. RESULTS | |
| 11 26 G-C or C-G pair structure_element Modeling a G-C or C-G pair at this position (i.e. 5’ G or 5’ C) suggests a 2-amino group in the minor groove would clash with the protein at G489 (Fig. 5a, Supplementary Fig. 7c). RESULTS | |
| 53 54 G residue_name Modeling a G-C or C-G pair at this position (i.e. 5’ G or 5’ C) suggests a 2-amino group in the minor groove would clash with the protein at G489 (Fig. 5a, Supplementary Fig. 7c). RESULTS | |
| 61 62 C residue_name Modeling a G-C or C-G pair at this position (i.e. 5’ G or 5’ C) suggests a 2-amino group in the minor groove would clash with the protein at G489 (Fig. 5a, Supplementary Fig. 7c). RESULTS | |
| 96 108 minor groove site Modeling a G-C or C-G pair at this position (i.e. 5’ G or 5’ C) suggests a 2-amino group in the minor groove would clash with the protein at G489 (Fig. 5a, Supplementary Fig. 7c). RESULTS | |
| 141 145 G489 residue_name_number Modeling a G-C or C-G pair at this position (i.e. 5’ G or 5’ C) suggests a 2-amino group in the minor groove would clash with the protein at G489 (Fig. 5a, Supplementary Fig. 7c). RESULTS | |
| 22 30 U-A pair structure_element Indeed, replacing the U-A pair adjacent to the editing site with a C-G pair in the Gli1 duplex substrate resulted in an 80% reduction in the rate of hADAR2d-catalyzed deamination (Figs. 5b, 5c). RESULTS | |
| 47 59 editing site site Indeed, replacing the U-A pair adjacent to the editing site with a C-G pair in the Gli1 duplex substrate resulted in an 80% reduction in the rate of hADAR2d-catalyzed deamination (Figs. 5b, 5c). RESULTS | |
| 67 75 C-G pair structure_element Indeed, replacing the U-A pair adjacent to the editing site with a C-G pair in the Gli1 duplex substrate resulted in an 80% reduction in the rate of hADAR2d-catalyzed deamination (Figs. 5b, 5c). RESULTS | |
| 83 87 Gli1 protein Indeed, replacing the U-A pair adjacent to the editing site with a C-G pair in the Gli1 duplex substrate resulted in an 80% reduction in the rate of hADAR2d-catalyzed deamination (Figs. 5b, 5c). RESULTS | |
| 149 156 hADAR2d mutant Indeed, replacing the U-A pair adjacent to the editing site with a C-G pair in the Gli1 duplex substrate resulted in an 80% reduction in the rate of hADAR2d-catalyzed deamination (Figs. 5b, 5c). RESULTS | |
| 176 184 U-A pair structure_element To determine whether this effect arises from an increase in local duplex stability from the C-G for U-A substitution or from the presence of the 2-amino group, we replaced the U-A pair with a U-2-aminopurine (2AP) pair. RESULTS | |
| 192 218 U-2-aminopurine (2AP) pair structure_element To determine whether this effect arises from an increase in local duplex stability from the C-G for U-A substitution or from the presence of the 2-amino group, we replaced the U-A pair with a U-2-aminopurine (2AP) pair. RESULTS | |
| 0 3 2AP structure_element 2AP is an adenosine analog that forms a base pair with uridine of similar stability to a U-A pair, but places an amino group in the minor groove (Fig. 5b). RESULTS | |
| 10 19 adenosine residue_name 2AP is an adenosine analog that forms a base pair with uridine of similar stability to a U-A pair, but places an amino group in the minor groove (Fig. 5b). RESULTS | |
| 55 62 uridine residue_name 2AP is an adenosine analog that forms a base pair with uridine of similar stability to a U-A pair, but places an amino group in the minor groove (Fig. 5b). RESULTS | |
| 89 97 U-A pair structure_element 2AP is an adenosine analog that forms a base pair with uridine of similar stability to a U-A pair, but places an amino group in the minor groove (Fig. 5b). RESULTS | |
| 132 144 minor groove site 2AP is an adenosine analog that forms a base pair with uridine of similar stability to a U-A pair, but places an amino group in the minor groove (Fig. 5b). RESULTS | |
| 136 148 minor groove site Importantly, this substitution also resulted in an 80% reduction in rate, illustrating the detrimental effect of the amino group in the minor groove at this location. RESULTS | |
| 32 38 hADAR2 protein These observations suggest that hADAR2’s 5’ nearest neighbor preference for U (or A) is due to a destabilizing clash with the protein backbone at G489 that results from the presence of an amino group in the minor groove at this location for sequences with 5’ nearest neighbor G or C. However, the observed clash is not severe and the enzyme would be able to accommodate G or C 5’ nearest neighbors by slight structural perturbations, explaining why this sequence preference is not an absolute requirement. RESULTS | |
| 76 77 U residue_name These observations suggest that hADAR2’s 5’ nearest neighbor preference for U (or A) is due to a destabilizing clash with the protein backbone at G489 that results from the presence of an amino group in the minor groove at this location for sequences with 5’ nearest neighbor G or C. However, the observed clash is not severe and the enzyme would be able to accommodate G or C 5’ nearest neighbors by slight structural perturbations, explaining why this sequence preference is not an absolute requirement. RESULTS | |
| 82 83 A residue_name These observations suggest that hADAR2’s 5’ nearest neighbor preference for U (or A) is due to a destabilizing clash with the protein backbone at G489 that results from the presence of an amino group in the minor groove at this location for sequences with 5’ nearest neighbor G or C. However, the observed clash is not severe and the enzyme would be able to accommodate G or C 5’ nearest neighbors by slight structural perturbations, explaining why this sequence preference is not an absolute requirement. RESULTS | |
| 146 150 G489 residue_name_number These observations suggest that hADAR2’s 5’ nearest neighbor preference for U (or A) is due to a destabilizing clash with the protein backbone at G489 that results from the presence of an amino group in the minor groove at this location for sequences with 5’ nearest neighbor G or C. However, the observed clash is not severe and the enzyme would be able to accommodate G or C 5’ nearest neighbors by slight structural perturbations, explaining why this sequence preference is not an absolute requirement. RESULTS | |
| 207 219 minor groove site These observations suggest that hADAR2’s 5’ nearest neighbor preference for U (or A) is due to a destabilizing clash with the protein backbone at G489 that results from the presence of an amino group in the minor groove at this location for sequences with 5’ nearest neighbor G or C. However, the observed clash is not severe and the enzyme would be able to accommodate G or C 5’ nearest neighbors by slight structural perturbations, explaining why this sequence preference is not an absolute requirement. RESULTS | |
| 276 277 G residue_name These observations suggest that hADAR2’s 5’ nearest neighbor preference for U (or A) is due to a destabilizing clash with the protein backbone at G489 that results from the presence of an amino group in the minor groove at this location for sequences with 5’ nearest neighbor G or C. However, the observed clash is not severe and the enzyme would be able to accommodate G or C 5’ nearest neighbors by slight structural perturbations, explaining why this sequence preference is not an absolute requirement. RESULTS | |
| 281 282 C residue_name These observations suggest that hADAR2’s 5’ nearest neighbor preference for U (or A) is due to a destabilizing clash with the protein backbone at G489 that results from the presence of an amino group in the minor groove at this location for sequences with 5’ nearest neighbor G or C. However, the observed clash is not severe and the enzyme would be able to accommodate G or C 5’ nearest neighbors by slight structural perturbations, explaining why this sequence preference is not an absolute requirement. RESULTS | |
| 370 371 G residue_name These observations suggest that hADAR2’s 5’ nearest neighbor preference for U (or A) is due to a destabilizing clash with the protein backbone at G489 that results from the presence of an amino group in the minor groove at this location for sequences with 5’ nearest neighbor G or C. However, the observed clash is not severe and the enzyme would be able to accommodate G or C 5’ nearest neighbors by slight structural perturbations, explaining why this sequence preference is not an absolute requirement. RESULTS | |
| 375 376 C residue_name These observations suggest that hADAR2’s 5’ nearest neighbor preference for U (or A) is due to a destabilizing clash with the protein backbone at G489 that results from the presence of an amino group in the minor groove at this location for sequences with 5’ nearest neighbor G or C. However, the observed clash is not severe and the enzyme would be able to accommodate G or C 5’ nearest neighbors by slight structural perturbations, explaining why this sequence preference is not an absolute requirement. RESULTS | |
| 15 26 hADAR2d-RNA complex_assembly In each of the hADAR2d-RNA structures reported here, the backbone carbonyl oxygen at S486 accepts an H-bond from the 2-amino group of the G on the 3’ side of the edited nucleotide (Fig. 5d). RESULTS | |
| 27 37 structures evidence In each of the hADAR2d-RNA structures reported here, the backbone carbonyl oxygen at S486 accepts an H-bond from the 2-amino group of the G on the 3’ side of the edited nucleotide (Fig. 5d). RESULTS | |
| 85 89 S486 residue_name_number In each of the hADAR2d-RNA structures reported here, the backbone carbonyl oxygen at S486 accepts an H-bond from the 2-amino group of the G on the 3’ side of the edited nucleotide (Fig. 5d). RESULTS | |
| 101 107 H-bond bond_interaction In each of the hADAR2d-RNA structures reported here, the backbone carbonyl oxygen at S486 accepts an H-bond from the 2-amino group of the G on the 3’ side of the edited nucleotide (Fig. 5d). RESULTS | |
| 138 139 G residue_name In each of the hADAR2d-RNA structures reported here, the backbone carbonyl oxygen at S486 accepts an H-bond from the 2-amino group of the G on the 3’ side of the edited nucleotide (Fig. 5d). RESULTS | |
| 0 7 Guanine residue_name Guanine is the only common nucleobase that presents an H-bond donor in the RNA minor groove suggesting that other nucleotides in this position would reduce editing efficiency. RESULTS | |
| 55 61 H-bond bond_interaction Guanine is the only common nucleobase that presents an H-bond donor in the RNA minor groove suggesting that other nucleotides in this position would reduce editing efficiency. RESULTS | |
| 75 91 RNA minor groove site Guanine is the only common nucleobase that presents an H-bond donor in the RNA minor groove suggesting that other nucleotides in this position would reduce editing efficiency. RESULTS | |
| 8 16 mutating experimental_method Indeed, mutating this base to A, C or U, while maintaining base pairing at this position, reduced the rate of deamination by hADAR2d in Gli1 mRNA model substrates (Supplementary Fig. 7 a–b). RESULTS | |
| 30 31 A residue_name Indeed, mutating this base to A, C or U, while maintaining base pairing at this position, reduced the rate of deamination by hADAR2d in Gli1 mRNA model substrates (Supplementary Fig. 7 a–b). RESULTS | |
| 33 34 C residue_name Indeed, mutating this base to A, C or U, while maintaining base pairing at this position, reduced the rate of deamination by hADAR2d in Gli1 mRNA model substrates (Supplementary Fig. 7 a–b). RESULTS | |
| 38 39 U residue_name Indeed, mutating this base to A, C or U, while maintaining base pairing at this position, reduced the rate of deamination by hADAR2d in Gli1 mRNA model substrates (Supplementary Fig. 7 a–b). RESULTS | |
| 125 132 hADAR2d mutant Indeed, mutating this base to A, C or U, while maintaining base pairing at this position, reduced the rate of deamination by hADAR2d in Gli1 mRNA model substrates (Supplementary Fig. 7 a–b). RESULTS | |
| 136 140 Gli1 protein Indeed, mutating this base to A, C or U, while maintaining base pairing at this position, reduced the rate of deamination by hADAR2d in Gli1 mRNA model substrates (Supplementary Fig. 7 a–b). RESULTS | |
| 141 145 mRNA chemical Indeed, mutating this base to A, C or U, while maintaining base pairing at this position, reduced the rate of deamination by hADAR2d in Gli1 mRNA model substrates (Supplementary Fig. 7 a–b). RESULTS | |
| 52 53 G residue_name To test the importance of the amino group on the 3’ G in the hADAR2d reaction, we prepared RNA duplex substrates with purine analogs on the 3’ side of the edited A (Fig. 5e). RESULTS | |
| 61 68 hADAR2d mutant To test the importance of the amino group on the 3’ G in the hADAR2d reaction, we prepared RNA duplex substrates with purine analogs on the 3’ side of the edited A (Fig. 5e). RESULTS | |
| 91 101 RNA duplex structure_element To test the importance of the amino group on the 3’ G in the hADAR2d reaction, we prepared RNA duplex substrates with purine analogs on the 3’ side of the edited A (Fig. 5e). RESULTS | |
| 155 161 edited protein_state To test the importance of the amino group on the 3’ G in the hADAR2d reaction, we prepared RNA duplex substrates with purine analogs on the 3’ side of the edited A (Fig. 5e). RESULTS | |
| 162 163 A residue_name To test the importance of the amino group on the 3’ G in the hADAR2d reaction, we prepared RNA duplex substrates with purine analogs on the 3’ side of the edited A (Fig. 5e). RESULTS | |
| 12 13 G residue_name We tested a G analog that lacks the 2-amino group (inosine, I) and one that blocks access to this amino group (N2-methylguanosine (N2MeG). RESULTS | |
| 51 58 inosine residue_name We tested a G analog that lacks the 2-amino group (inosine, I) and one that blocks access to this amino group (N2-methylguanosine (N2MeG). RESULTS | |
| 60 61 I residue_name We tested a G analog that lacks the 2-amino group (inosine, I) and one that blocks access to this amino group (N2-methylguanosine (N2MeG). RESULTS | |
| 30 31 A residue_name In addition, we compared a 3’ A to a 3’ 2AP since 2AP could form the H-bonding interaction observed with S486. RESULTS | |
| 40 43 2AP structure_element In addition, we compared a 3’ A to a 3’ 2AP since 2AP could form the H-bonding interaction observed with S486. RESULTS | |
| 50 53 2AP structure_element In addition, we compared a 3’ A to a 3’ 2AP since 2AP could form the H-bonding interaction observed with S486. RESULTS | |
| 69 90 H-bonding interaction bond_interaction In addition, we compared a 3’ A to a 3’ 2AP since 2AP could form the H-bonding interaction observed with S486. RESULTS | |
| 105 109 S486 residue_name_number In addition, we compared a 3’ A to a 3’ 2AP since 2AP could form the H-bonding interaction observed with S486. RESULTS | |
| 59 66 hADAR2d mutant We found the substrate with a 3’ N2MeG to be unreactive to hADAR2d-catalyzed deamination confirming the importance of the observed close approach by the protein to the 3’ G 2-amino group (Fig. 5f). RESULTS | |
| 171 172 G residue_name We found the substrate with a 3’ N2MeG to be unreactive to hADAR2d-catalyzed deamination confirming the importance of the observed close approach by the protein to the 3’ G 2-amino group (Fig. 5f). RESULTS | |
| 37 38 I residue_name In addition, the substrate with a 3’ I displayed a reduced deamination rate compared to the substrate with a 3’ G suggesting the observed H-bond to the 2-amino group contributes to the 3’ nearest neighbor selectivity (Fig. 5f). RESULTS | |
| 51 75 reduced deamination rate evidence In addition, the substrate with a 3’ I displayed a reduced deamination rate compared to the substrate with a 3’ G suggesting the observed H-bond to the 2-amino group contributes to the 3’ nearest neighbor selectivity (Fig. 5f). RESULTS | |
| 112 113 G residue_name In addition, the substrate with a 3’ I displayed a reduced deamination rate compared to the substrate with a 3’ G suggesting the observed H-bond to the 2-amino group contributes to the 3’ nearest neighbor selectivity (Fig. 5f). RESULTS | |
| 138 144 H-bond bond_interaction In addition, the substrate with a 3’ I displayed a reduced deamination rate compared to the substrate with a 3’ G suggesting the observed H-bond to the 2-amino group contributes to the 3’ nearest neighbor selectivity (Fig. 5f). RESULTS | |
| 100 103 2AP structure_element This conclusion is further supported by the observation that deamination in the substrate with a 3’ 2AP is faster than in the substrate with a 3’ A (Fig. 5f). RESULTS | |
| 146 147 A residue_name This conclusion is further supported by the observation that deamination in the substrate with a 3’ 2AP is faster than in the substrate with a 3’ A (Fig. 5f). RESULTS | |
| 0 17 RNA-binding loops structure_element RNA-binding loops of the ADAR catalytic domain RESULTS | |
| 25 29 ADAR protein_type RNA-binding loops of the ADAR catalytic domain RESULTS | |
| 30 46 catalytic domain structure_element RNA-binding loops of the ADAR catalytic domain RESULTS | |
| 4 14 structures evidence The structures reported here identify RNA-binding loops of the ADAR catalytic domain and suggest roles for several amino acids not previously known to be important for editing, either substrate binding or catalysis (Fig. 6). RESULTS | |
| 38 55 RNA-binding loops structure_element The structures reported here identify RNA-binding loops of the ADAR catalytic domain and suggest roles for several amino acids not previously known to be important for editing, either substrate binding or catalysis (Fig. 6). RESULTS | |
| 63 67 ADAR protein_type The structures reported here identify RNA-binding loops of the ADAR catalytic domain and suggest roles for several amino acids not previously known to be important for editing, either substrate binding or catalysis (Fig. 6). RESULTS | |
| 68 84 catalytic domain structure_element The structures reported here identify RNA-binding loops of the ADAR catalytic domain and suggest roles for several amino acids not previously known to be important for editing, either substrate binding or catalysis (Fig. 6). RESULTS | |
| 19 23 R510 residue_name_number The side chain for R510 ion-pairs with the 3’ phosphodiester of the orphaned nucleotide (Figs. 3a, 3c). RESULTS | |
| 24 33 ion-pairs bond_interaction The side chain for R510 ion-pairs with the 3’ phosphodiester of the orphaned nucleotide (Figs. 3a, 3c). RESULTS | |
| 68 76 orphaned protein_state The side chain for R510 ion-pairs with the 3’ phosphodiester of the orphaned nucleotide (Figs. 3a, 3c). RESULTS | |
| 77 87 nucleotide chemical The side chain for R510 ion-pairs with the 3’ phosphodiester of the orphaned nucleotide (Figs. 3a, 3c). RESULTS | |
| 16 25 conserved protein_state This residue is conserved in ADAR2s and ADAR1s, but is glutamine in the editing-inactive ADAR3s (Supplementary Table 1). RESULTS | |
| 29 35 ADAR2s protein_type This residue is conserved in ADAR2s and ADAR1s, but is glutamine in the editing-inactive ADAR3s (Supplementary Table 1). RESULTS | |
| 40 46 ADAR1s protein_type This residue is conserved in ADAR2s and ADAR1s, but is glutamine in the editing-inactive ADAR3s (Supplementary Table 1). RESULTS | |
| 55 64 glutamine residue_name This residue is conserved in ADAR2s and ADAR1s, but is glutamine in the editing-inactive ADAR3s (Supplementary Table 1). RESULTS | |
| 72 88 editing-inactive protein_state This residue is conserved in ADAR2s and ADAR1s, but is glutamine in the editing-inactive ADAR3s (Supplementary Table 1). RESULTS | |
| 89 95 ADAR3s protein_type This residue is conserved in ADAR2s and ADAR1s, but is glutamine in the editing-inactive ADAR3s (Supplementary Table 1). RESULTS | |
| 0 8 Mutation experimental_method Mutation of hADAR2d at this site to either glutamine (R510Q) or to alanine (R510A) reduced the measured deamination rate constant by approximately an order of magnitude (Fig. 6c). RESULTS | |
| 12 19 hADAR2d mutant Mutation of hADAR2d at this site to either glutamine (R510Q) or to alanine (R510A) reduced the measured deamination rate constant by approximately an order of magnitude (Fig. 6c). RESULTS | |
| 43 52 glutamine residue_name Mutation of hADAR2d at this site to either glutamine (R510Q) or to alanine (R510A) reduced the measured deamination rate constant by approximately an order of magnitude (Fig. 6c). RESULTS | |
| 54 59 R510Q mutant Mutation of hADAR2d at this site to either glutamine (R510Q) or to alanine (R510A) reduced the measured deamination rate constant by approximately an order of magnitude (Fig. 6c). RESULTS | |
| 67 74 alanine residue_name Mutation of hADAR2d at this site to either glutamine (R510Q) or to alanine (R510A) reduced the measured deamination rate constant by approximately an order of magnitude (Fig. 6c). RESULTS | |
| 76 81 R510A mutant Mutation of hADAR2d at this site to either glutamine (R510Q) or to alanine (R510A) reduced the measured deamination rate constant by approximately an order of magnitude (Fig. 6c). RESULTS | |
| 104 129 deamination rate constant evidence Mutation of hADAR2d at this site to either glutamine (R510Q) or to alanine (R510A) reduced the measured deamination rate constant by approximately an order of magnitude (Fig. 6c). RESULTS | |
| 79 83 G593 residue_name_number In addition, the contact point near the 5’ end of the unedited strand involves G593, K594 and R348, residues completely conserved in the family of ADAR2s (Fig. 2c, Supplementary Table 1). RESULTS | |
| 85 89 K594 residue_name_number In addition, the contact point near the 5’ end of the unedited strand involves G593, K594 and R348, residues completely conserved in the family of ADAR2s (Fig. 2c, Supplementary Table 1). RESULTS | |
| 94 98 R348 residue_name_number In addition, the contact point near the 5’ end of the unedited strand involves G593, K594 and R348, residues completely conserved in the family of ADAR2s (Fig. 2c, Supplementary Table 1). RESULTS | |
| 109 129 completely conserved protein_state In addition, the contact point near the 5’ end of the unedited strand involves G593, K594 and R348, residues completely conserved in the family of ADAR2s (Fig. 2c, Supplementary Table 1). RESULTS | |
| 147 153 ADAR2s protein_type In addition, the contact point near the 5’ end of the unedited strand involves G593, K594 and R348, residues completely conserved in the family of ADAR2s (Fig. 2c, Supplementary Table 1). RESULTS | |
| 0 8 Mutation experimental_method Mutation of any of these residues to alanine (G593A, K594A, R348A) substantially reduces editing activity (Fig. 6c). RESULTS | |
| 37 44 alanine residue_name Mutation of any of these residues to alanine (G593A, K594A, R348A) substantially reduces editing activity (Fig. 6c). RESULTS | |
| 46 51 G593A mutant Mutation of any of these residues to alanine (G593A, K594A, R348A) substantially reduces editing activity (Fig. 6c). RESULTS | |
| 53 58 K594A mutant Mutation of any of these residues to alanine (G593A, K594A, R348A) substantially reduces editing activity (Fig. 6c). RESULTS | |
| 60 65 R348A mutant Mutation of any of these residues to alanine (G593A, K594A, R348A) substantially reduces editing activity (Fig. 6c). RESULTS | |
| 13 21 mutation experimental_method In addition, mutation of G593 to glutamic acid (G593E) resulted in a nearly two orders of magnitude reduction in rate, consistent with proximity of this residue to the negatively charged phosphodiester backbone of the RNA (Fig. 6c). RESULTS | |
| 25 29 G593 residue_name_number In addition, mutation of G593 to glutamic acid (G593E) resulted in a nearly two orders of magnitude reduction in rate, consistent with proximity of this residue to the negatively charged phosphodiester backbone of the RNA (Fig. 6c). RESULTS | |
| 33 46 glutamic acid residue_name In addition, mutation of G593 to glutamic acid (G593E) resulted in a nearly two orders of magnitude reduction in rate, consistent with proximity of this residue to the negatively charged phosphodiester backbone of the RNA (Fig. 6c). RESULTS | |
| 48 53 G593E mutant In addition, mutation of G593 to glutamic acid (G593E) resulted in a nearly two orders of magnitude reduction in rate, consistent with proximity of this residue to the negatively charged phosphodiester backbone of the RNA (Fig. 6c). RESULTS | |
| 218 221 RNA chemical In addition, mutation of G593 to glutamic acid (G593E) resulted in a nearly two orders of magnitude reduction in rate, consistent with proximity of this residue to the negatively charged phosphodiester backbone of the RNA (Fig. 6c). RESULTS | |
| 0 3 RNA chemical RNA binding leads to an ordering of the 454–477 loop, which was disordered in the RNA-free hADAR2d structure (Fig. 1d, green) (Supplementary Video 2). RESULTS | |
| 40 47 454–477 residue_range RNA binding leads to an ordering of the 454–477 loop, which was disordered in the RNA-free hADAR2d structure (Fig. 1d, green) (Supplementary Video 2). RESULTS | |
| 48 52 loop structure_element RNA binding leads to an ordering of the 454–477 loop, which was disordered in the RNA-free hADAR2d structure (Fig. 1d, green) (Supplementary Video 2). RESULTS | |
| 64 74 disordered protein_state RNA binding leads to an ordering of the 454–477 loop, which was disordered in the RNA-free hADAR2d structure (Fig. 1d, green) (Supplementary Video 2). RESULTS | |
| 82 90 RNA-free protein_state RNA binding leads to an ordering of the 454–477 loop, which was disordered in the RNA-free hADAR2d structure (Fig. 1d, green) (Supplementary Video 2). RESULTS | |
| 91 98 hADAR2d mutant RNA binding leads to an ordering of the 454–477 loop, which was disordered in the RNA-free hADAR2d structure (Fig. 1d, green) (Supplementary Video 2). RESULTS | |
| 99 108 structure evidence RNA binding leads to an ordering of the 454–477 loop, which was disordered in the RNA-free hADAR2d structure (Fig. 1d, green) (Supplementary Video 2). RESULTS | |
| 5 9 loop structure_element This loop binds the RNA duplex contacting the minor groove near the editing site and inserting into the adjacent major groove (Fig. 6e). RESULTS | |
| 20 30 RNA duplex structure_element This loop binds the RNA duplex contacting the minor groove near the editing site and inserting into the adjacent major groove (Fig. 6e). RESULTS | |
| 46 58 minor groove site This loop binds the RNA duplex contacting the minor groove near the editing site and inserting into the adjacent major groove (Fig. 6e). RESULTS | |
| 68 80 editing site site This loop binds the RNA duplex contacting the minor groove near the editing site and inserting into the adjacent major groove (Fig. 6e). RESULTS | |
| 113 125 major groove site This loop binds the RNA duplex contacting the minor groove near the editing site and inserting into the adjacent major groove (Fig. 6e). RESULTS | |
| 5 9 loop structure_element This loop sequence is conserved in ADAR2s but different in the family of ADAR1s (Fig. 6d). RESULTS | |
| 22 31 conserved protein_state This loop sequence is conserved in ADAR2s but different in the family of ADAR1s (Fig. 6d). RESULTS | |
| 35 41 ADAR2s protein_type This loop sequence is conserved in ADAR2s but different in the family of ADAR1s (Fig. 6d). RESULTS | |
| 73 79 ADAR1s protein_type This loop sequence is conserved in ADAR2s but different in the family of ADAR1s (Fig. 6d). RESULTS | |
| 51 56 ADARs protein_type The substantial difference in sequence between the ADARs in this RNA-binding loop suggests differences in editing site selectivity between the two ADARs arise, at least in part, from differences in how this loop binds RNA substrates. RESULTS | |
| 65 81 RNA-binding loop structure_element The substantial difference in sequence between the ADARs in this RNA-binding loop suggests differences in editing site selectivity between the two ADARs arise, at least in part, from differences in how this loop binds RNA substrates. RESULTS | |
| 106 118 editing site site The substantial difference in sequence between the ADARs in this RNA-binding loop suggests differences in editing site selectivity between the two ADARs arise, at least in part, from differences in how this loop binds RNA substrates. RESULTS | |
| 147 152 ADARs protein_type The substantial difference in sequence between the ADARs in this RNA-binding loop suggests differences in editing site selectivity between the two ADARs arise, at least in part, from differences in how this loop binds RNA substrates. RESULTS | |
| 207 211 loop structure_element The substantial difference in sequence between the ADARs in this RNA-binding loop suggests differences in editing site selectivity between the two ADARs arise, at least in part, from differences in how this loop binds RNA substrates. RESULTS | |
| 218 221 RNA chemical The substantial difference in sequence between the ADARs in this RNA-binding loop suggests differences in editing site selectivity between the two ADARs arise, at least in part, from differences in how this loop binds RNA substrates. RESULTS | |
| 57 87 nucleic acid modifying enzymes protein_type Base flipping is a well-characterized mechanism by which nucleic acid modifying enzymes gain access to sites of reaction that are otherwise buried in base-paired structures. DISCUSS | |
| 162 172 structures evidence Base flipping is a well-characterized mechanism by which nucleic acid modifying enzymes gain access to sites of reaction that are otherwise buried in base-paired structures. DISCUSS | |
| 0 14 DNA methylases protein_type DNA methylases, DNA repair glycosylases and RNA loop modifying enzymes are known that flip a nucleotide out of a base pair. DISCUSS | |
| 16 39 DNA repair glycosylases protein_type DNA methylases, DNA repair glycosylases and RNA loop modifying enzymes are known that flip a nucleotide out of a base pair. DISCUSS | |
| 44 70 RNA loop modifying enzymes protein_type DNA methylases, DNA repair glycosylases and RNA loop modifying enzymes are known that flip a nucleotide out of a base pair. DISCUSS | |
| 93 103 nucleotide chemical DNA methylases, DNA repair glycosylases and RNA loop modifying enzymes are known that flip a nucleotide out of a base pair. DISCUSS | |
| 48 69 base-flipping enzymes protein_type However, none of the structurally characterized base-flipping enzymes access their reactive sites from within a normal base-paired RNA duplex. DISCUSS | |
| 83 97 reactive sites site However, none of the structurally characterized base-flipping enzymes access their reactive sites from within a normal base-paired RNA duplex. DISCUSS | |
| 112 130 normal base-paired protein_state However, none of the structurally characterized base-flipping enzymes access their reactive sites from within a normal base-paired RNA duplex. DISCUSS | |
| 131 141 RNA duplex structure_element However, none of the structurally characterized base-flipping enzymes access their reactive sites from within a normal base-paired RNA duplex. DISCUSS | |
| 70 80 RNA duplex structure_element We are aware of one other protein-induced nucleotide flipping from an RNA duplex region. DISCUSS | |
| 0 9 Bacterial taxonomy_domain Bacterial initiation factor 1 (IF1) binds to the 30S ribosomal subunit at helix 44 of 16S RNA with A1492 and A1493 flipped out of the helix and bound into protein pockets (Supplementary Fig. 5b). DISCUSS | |
| 10 29 initiation factor 1 protein Bacterial initiation factor 1 (IF1) binds to the 30S ribosomal subunit at helix 44 of 16S RNA with A1492 and A1493 flipped out of the helix and bound into protein pockets (Supplementary Fig. 5b). DISCUSS | |
| 31 34 IF1 protein Bacterial initiation factor 1 (IF1) binds to the 30S ribosomal subunit at helix 44 of 16S RNA with A1492 and A1493 flipped out of the helix and bound into protein pockets (Supplementary Fig. 5b). DISCUSS | |
| 49 70 30S ribosomal subunit complex_assembly Bacterial initiation factor 1 (IF1) binds to the 30S ribosomal subunit at helix 44 of 16S RNA with A1492 and A1493 flipped out of the helix and bound into protein pockets (Supplementary Fig. 5b). DISCUSS | |
| 74 82 helix 44 structure_element Bacterial initiation factor 1 (IF1) binds to the 30S ribosomal subunit at helix 44 of 16S RNA with A1492 and A1493 flipped out of the helix and bound into protein pockets (Supplementary Fig. 5b). DISCUSS | |
| 86 93 16S RNA chemical Bacterial initiation factor 1 (IF1) binds to the 30S ribosomal subunit at helix 44 of 16S RNA with A1492 and A1493 flipped out of the helix and bound into protein pockets (Supplementary Fig. 5b). DISCUSS | |
| 99 104 A1492 residue_name_number Bacterial initiation factor 1 (IF1) binds to the 30S ribosomal subunit at helix 44 of 16S RNA with A1492 and A1493 flipped out of the helix and bound into protein pockets (Supplementary Fig. 5b). DISCUSS | |
| 109 114 A1493 residue_name_number Bacterial initiation factor 1 (IF1) binds to the 30S ribosomal subunit at helix 44 of 16S RNA with A1492 and A1493 flipped out of the helix and bound into protein pockets (Supplementary Fig. 5b). DISCUSS | |
| 115 126 flipped out protein_state Bacterial initiation factor 1 (IF1) binds to the 30S ribosomal subunit at helix 44 of 16S RNA with A1492 and A1493 flipped out of the helix and bound into protein pockets (Supplementary Fig. 5b). DISCUSS | |
| 144 154 bound into protein_state Bacterial initiation factor 1 (IF1) binds to the 30S ribosomal subunit at helix 44 of 16S RNA with A1492 and A1493 flipped out of the helix and bound into protein pockets (Supplementary Fig. 5b). DISCUSS | |
| 155 170 protein pockets site Bacterial initiation factor 1 (IF1) binds to the 30S ribosomal subunit at helix 44 of 16S RNA with A1492 and A1493 flipped out of the helix and bound into protein pockets (Supplementary Fig. 5b). DISCUSS | |
| 44 60 highly distorted protein_state However, these nucleotides are located in a highly distorted and dynamic duplex region containing several mismatches and are predisposed to undergo this conformational change. DISCUSS | |
| 65 72 dynamic protein_state However, these nucleotides are located in a highly distorted and dynamic duplex region containing several mismatches and are predisposed to undergo this conformational change. DISCUSS | |
| 73 86 duplex region structure_element However, these nucleotides are located in a highly distorted and dynamic duplex region containing several mismatches and are predisposed to undergo this conformational change. DISCUSS | |
| 62 68 normal protein_state Thus, this system is not illustrative of base flipping from a normal duplex and does not involve an enzyme that must carryout a chemical reaction on the flipped out nucleotide. DISCUSS | |
| 153 164 flipped out protein_state Thus, this system is not illustrative of base flipping from a normal duplex and does not involve an enzyme that must carryout a chemical reaction on the flipped out nucleotide. DISCUSS | |
| 165 175 nucleotide chemical Thus, this system is not illustrative of base flipping from a normal duplex and does not involve an enzyme that must carryout a chemical reaction on the flipped out nucleotide. DISCUSS | |
| 6 30 RNA modification enzymes protein_type Other RNA modification enzymes are known that flip nucleotides out of loops, even from base pairs in loop regions (pseudoU synthetase, tRNA transglycosylase, and restrictocin bound to sarcin/ricin loop of 28S rRNA) (Supplementary Fig. 5b). DISCUSS | |
| 115 133 pseudoU synthetase protein_type Other RNA modification enzymes are known that flip nucleotides out of loops, even from base pairs in loop regions (pseudoU synthetase, tRNA transglycosylase, and restrictocin bound to sarcin/ricin loop of 28S rRNA) (Supplementary Fig. 5b). DISCUSS | |
| 135 156 tRNA transglycosylase protein_type Other RNA modification enzymes are known that flip nucleotides out of loops, even from base pairs in loop regions (pseudoU synthetase, tRNA transglycosylase, and restrictocin bound to sarcin/ricin loop of 28S rRNA) (Supplementary Fig. 5b). DISCUSS | |
| 162 174 restrictocin protein Other RNA modification enzymes are known that flip nucleotides out of loops, even from base pairs in loop regions (pseudoU synthetase, tRNA transglycosylase, and restrictocin bound to sarcin/ricin loop of 28S rRNA) (Supplementary Fig. 5b). DISCUSS | |
| 175 183 bound to protein_state Other RNA modification enzymes are known that flip nucleotides out of loops, even from base pairs in loop regions (pseudoU synthetase, tRNA transglycosylase, and restrictocin bound to sarcin/ricin loop of 28S rRNA) (Supplementary Fig. 5b). DISCUSS | |
| 184 201 sarcin/ricin loop structure_element Other RNA modification enzymes are known that flip nucleotides out of loops, even from base pairs in loop regions (pseudoU synthetase, tRNA transglycosylase, and restrictocin bound to sarcin/ricin loop of 28S rRNA) (Supplementary Fig. 5b). DISCUSS | |
| 205 213 28S rRNA chemical Other RNA modification enzymes are known that flip nucleotides out of loops, even from base pairs in loop regions (pseudoU synthetase, tRNA transglycosylase, and restrictocin bound to sarcin/ricin loop of 28S rRNA) (Supplementary Fig. 5b). DISCUSS | |
| 12 30 modification sites site Because the modification sites are not flanked on both sides by normal duplex, these enzymes do not experience the same limits in approach to the substrate that ADARs do. DISCUSS | |
| 64 70 normal protein_state Because the modification sites are not flanked on both sides by normal duplex, these enzymes do not experience the same limits in approach to the substrate that ADARs do. DISCUSS | |
| 71 77 duplex structure_element Because the modification sites are not flanked on both sides by normal duplex, these enzymes do not experience the same limits in approach to the substrate that ADARs do. DISCUSS | |
| 161 166 ADARs protein_type Because the modification sites are not flanked on both sides by normal duplex, these enzymes do not experience the same limits in approach to the substrate that ADARs do. DISCUSS | |
| 14 19 ADARs protein_type The fact that ADARs must induce flipping from a normal duplex has implications on its preference for adenosines flanked by certain base pairs, a phenomenon that was not well understood prior to this work. DISCUSS | |
| 48 54 normal protein_state The fact that ADARs must induce flipping from a normal duplex has implications on its preference for adenosines flanked by certain base pairs, a phenomenon that was not well understood prior to this work. DISCUSS | |
| 55 61 duplex structure_element The fact that ADARs must induce flipping from a normal duplex has implications on its preference for adenosines flanked by certain base pairs, a phenomenon that was not well understood prior to this work. DISCUSS | |
| 101 111 adenosines residue_name The fact that ADARs must induce flipping from a normal duplex has implications on its preference for adenosines flanked by certain base pairs, a phenomenon that was not well understood prior to this work. DISCUSS | |
| 7 17 structures evidence In our structures, the flipped out 8-azanebularine is hydrated, mimicking the tetrahedral intermediate predicted for deamination of adenosine (Figs. 1b, 3a, Supplementary Fig. 3 a–b). DISCUSS | |
| 23 34 flipped out protein_state In our structures, the flipped out 8-azanebularine is hydrated, mimicking the tetrahedral intermediate predicted for deamination of adenosine (Figs. 1b, 3a, Supplementary Fig. 3 a–b). DISCUSS | |
| 35 50 8-azanebularine chemical In our structures, the flipped out 8-azanebularine is hydrated, mimicking the tetrahedral intermediate predicted for deamination of adenosine (Figs. 1b, 3a, Supplementary Fig. 3 a–b). DISCUSS | |
| 132 141 adenosine residue_name In our structures, the flipped out 8-azanebularine is hydrated, mimicking the tetrahedral intermediate predicted for deamination of adenosine (Figs. 1b, 3a, Supplementary Fig. 3 a–b). DISCUSS | |
| 11 26 8-azanebularine chemical Our use of 8-azanebularine, with its high propensity to form a covalent hydrate, allowed us to capture a true mimic of the tetrahedral intermediate and reveal the interactions between the deaminase active site and the reactive nucleotide. DISCUSS | |
| 188 197 deaminase protein_type Our use of 8-azanebularine, with its high propensity to form a covalent hydrate, allowed us to capture a true mimic of the tetrahedral intermediate and reveal the interactions between the deaminase active site and the reactive nucleotide. DISCUSS | |
| 198 209 active site site Our use of 8-azanebularine, with its high propensity to form a covalent hydrate, allowed us to capture a true mimic of the tetrahedral intermediate and reveal the interactions between the deaminase active site and the reactive nucleotide. DISCUSS | |
| 13 28 8-azanebularine chemical In addition, 8-azanebularine was found to adopt a 2’-endo sugar pucker with its 2’-hydroxyl H-bonded to the protein backbone carbonyl at T375. DISCUSS | |
| 92 100 H-bonded bond_interaction In addition, 8-azanebularine was found to adopt a 2’-endo sugar pucker with its 2’-hydroxyl H-bonded to the protein backbone carbonyl at T375. DISCUSS | |
| 137 141 T375 residue_name_number In addition, 8-azanebularine was found to adopt a 2’-endo sugar pucker with its 2’-hydroxyl H-bonded to the protein backbone carbonyl at T375. DISCUSS | |
| 79 83 zinc chemical The 2’ endo conformation appears to facilitate access of the nucleobase to the zinc-bound water for nucleophilic attack at C6. DISCUSS | |
| 90 95 water chemical The 2’ endo conformation appears to facilitate access of the nucleobase to the zinc-bound water for nucleophilic attack at C6. DISCUSS | |
| 14 35 base-flipping enzymes protein_type Several other base-flipping enzymes stabilize the altered nucleic acid conformation by intercalation of an amino acid side chain into the space vacated by the flipped out base. DISCUSS | |
| 159 170 flipped out protein_state Several other base-flipping enzymes stabilize the altered nucleic acid conformation by intercalation of an amino acid side chain into the space vacated by the flipped out base. DISCUSS | |
| 171 175 base chemical Several other base-flipping enzymes stabilize the altered nucleic acid conformation by intercalation of an amino acid side chain into the space vacated by the flipped out base. DISCUSS | |
| 4 10 hADAR2 protein For hADAR2, E488 serves this role. DISCUSS | |
| 12 16 E488 residue_name_number For hADAR2, E488 serves this role. DISCUSS | |
| 11 21 structures evidence In the two structures with wild type hADAR2, the E488 residue and orphan base are in nearly identical positions (see Supplementary Fig. 4a for overlay). DISCUSS | |
| 27 36 wild type protein_state In the two structures with wild type hADAR2, the E488 residue and orphan base are in nearly identical positions (see Supplementary Fig. 4a for overlay). DISCUSS | |
| 37 43 hADAR2 protein In the two structures with wild type hADAR2, the E488 residue and orphan base are in nearly identical positions (see Supplementary Fig. 4a for overlay). DISCUSS | |
| 49 53 E488 residue_name_number In the two structures with wild type hADAR2, the E488 residue and orphan base are in nearly identical positions (see Supplementary Fig. 4a for overlay). DISCUSS | |
| 66 72 orphan protein_state In the two structures with wild type hADAR2, the E488 residue and orphan base are in nearly identical positions (see Supplementary Fig. 4a for overlay). DISCUSS | |
| 73 77 base chemical In the two structures with wild type hADAR2, the E488 residue and orphan base are in nearly identical positions (see Supplementary Fig. 4a for overlay). DISCUSS | |
| 143 150 overlay experimental_method In the two structures with wild type hADAR2, the E488 residue and orphan base are in nearly identical positions (see Supplementary Fig. 4a for overlay). DISCUSS | |
| 10 14 E488 residue_name_number Thus, the E488 side chain directly contacts each orphan base, likely by accepting an H-bond from uracil N3H or by donating an H-bond to cytidine N3. DISCUSS | |
| 49 55 orphan protein_state Thus, the E488 side chain directly contacts each orphan base, likely by accepting an H-bond from uracil N3H or by donating an H-bond to cytidine N3. DISCUSS | |
| 56 60 base chemical Thus, the E488 side chain directly contacts each orphan base, likely by accepting an H-bond from uracil N3H or by donating an H-bond to cytidine N3. DISCUSS | |
| 85 91 H-bond bond_interaction Thus, the E488 side chain directly contacts each orphan base, likely by accepting an H-bond from uracil N3H or by donating an H-bond to cytidine N3. DISCUSS | |
| 97 103 uracil residue_name Thus, the E488 side chain directly contacts each orphan base, likely by accepting an H-bond from uracil N3H or by donating an H-bond to cytidine N3. DISCUSS | |
| 126 132 H-bond bond_interaction Thus, the E488 side chain directly contacts each orphan base, likely by accepting an H-bond from uracil N3H or by donating an H-bond to cytidine N3. DISCUSS | |
| 136 144 cytidine residue_name Thus, the E488 side chain directly contacts each orphan base, likely by accepting an H-bond from uracil N3H or by donating an H-bond to cytidine N3. DISCUSS | |
| 32 36 E488 residue_name_number The latter interaction requires E488 to be protonated. DISCUSS | |
| 43 53 protonated protein_state The latter interaction requires E488 to be protonated. DISCUSS | |
| 4 7 pKa evidence The pKa of E488 in the ADAR-RNA complex has not been measured, but proximity to H-bond acceptors, such as cytidine N3, and insertion between stacked nucleobases, would undoubtedly elevate this value and could lead to a substantial fraction in the protonated state at physiologically relevant pH. Since the glutamine side chain is fully protonated under physiologically relevant conditions, a rate enhancement for the E488Q mutant would be expected if the reaction requires E488 protonation. DISCUSS | |
| 11 15 E488 residue_name_number The pKa of E488 in the ADAR-RNA complex has not been measured, but proximity to H-bond acceptors, such as cytidine N3, and insertion between stacked nucleobases, would undoubtedly elevate this value and could lead to a substantial fraction in the protonated state at physiologically relevant pH. Since the glutamine side chain is fully protonated under physiologically relevant conditions, a rate enhancement for the E488Q mutant would be expected if the reaction requires E488 protonation. DISCUSS | |
| 23 31 ADAR-RNA complex_assembly The pKa of E488 in the ADAR-RNA complex has not been measured, but proximity to H-bond acceptors, such as cytidine N3, and insertion between stacked nucleobases, would undoubtedly elevate this value and could lead to a substantial fraction in the protonated state at physiologically relevant pH. Since the glutamine side chain is fully protonated under physiologically relevant conditions, a rate enhancement for the E488Q mutant would be expected if the reaction requires E488 protonation. DISCUSS | |
| 80 86 H-bond bond_interaction The pKa of E488 in the ADAR-RNA complex has not been measured, but proximity to H-bond acceptors, such as cytidine N3, and insertion between stacked nucleobases, would undoubtedly elevate this value and could lead to a substantial fraction in the protonated state at physiologically relevant pH. Since the glutamine side chain is fully protonated under physiologically relevant conditions, a rate enhancement for the E488Q mutant would be expected if the reaction requires E488 protonation. DISCUSS | |
| 106 114 cytidine residue_name The pKa of E488 in the ADAR-RNA complex has not been measured, but proximity to H-bond acceptors, such as cytidine N3, and insertion between stacked nucleobases, would undoubtedly elevate this value and could lead to a substantial fraction in the protonated state at physiologically relevant pH. Since the glutamine side chain is fully protonated under physiologically relevant conditions, a rate enhancement for the E488Q mutant would be expected if the reaction requires E488 protonation. DISCUSS | |
| 247 257 protonated protein_state The pKa of E488 in the ADAR-RNA complex has not been measured, but proximity to H-bond acceptors, such as cytidine N3, and insertion between stacked nucleobases, would undoubtedly elevate this value and could lead to a substantial fraction in the protonated state at physiologically relevant pH. Since the glutamine side chain is fully protonated under physiologically relevant conditions, a rate enhancement for the E488Q mutant would be expected if the reaction requires E488 protonation. DISCUSS | |
| 306 315 glutamine residue_name The pKa of E488 in the ADAR-RNA complex has not been measured, but proximity to H-bond acceptors, such as cytidine N3, and insertion between stacked nucleobases, would undoubtedly elevate this value and could lead to a substantial fraction in the protonated state at physiologically relevant pH. Since the glutamine side chain is fully protonated under physiologically relevant conditions, a rate enhancement for the E488Q mutant would be expected if the reaction requires E488 protonation. DISCUSS | |
| 330 346 fully protonated protein_state The pKa of E488 in the ADAR-RNA complex has not been measured, but proximity to H-bond acceptors, such as cytidine N3, and insertion between stacked nucleobases, would undoubtedly elevate this value and could lead to a substantial fraction in the protonated state at physiologically relevant pH. Since the glutamine side chain is fully protonated under physiologically relevant conditions, a rate enhancement for the E488Q mutant would be expected if the reaction requires E488 protonation. DISCUSS | |
| 417 422 E488Q mutant The pKa of E488 in the ADAR-RNA complex has not been measured, but proximity to H-bond acceptors, such as cytidine N3, and insertion between stacked nucleobases, would undoubtedly elevate this value and could lead to a substantial fraction in the protonated state at physiologically relevant pH. Since the glutamine side chain is fully protonated under physiologically relevant conditions, a rate enhancement for the E488Q mutant would be expected if the reaction requires E488 protonation. DISCUSS | |
| 423 429 mutant protein_state The pKa of E488 in the ADAR-RNA complex has not been measured, but proximity to H-bond acceptors, such as cytidine N3, and insertion between stacked nucleobases, would undoubtedly elevate this value and could lead to a substantial fraction in the protonated state at physiologically relevant pH. Since the glutamine side chain is fully protonated under physiologically relevant conditions, a rate enhancement for the E488Q mutant would be expected if the reaction requires E488 protonation. DISCUSS | |
| 473 477 E488 residue_name_number The pKa of E488 in the ADAR-RNA complex has not been measured, but proximity to H-bond acceptors, such as cytidine N3, and insertion between stacked nucleobases, would undoubtedly elevate this value and could lead to a substantial fraction in the protonated state at physiologically relevant pH. Since the glutamine side chain is fully protonated under physiologically relevant conditions, a rate enhancement for the E488Q mutant would be expected if the reaction requires E488 protonation. DISCUSS | |
| 20 27 hADAR2d mutant The interactions of hADAR2d with base pairs adjacent to the editing site adenosine explain the known 5’ and 3’ nearest neighbor preferences (Fig. 5). DISCUSS | |
| 60 72 editing site site The interactions of hADAR2d with base pairs adjacent to the editing site adenosine explain the known 5’ and 3’ nearest neighbor preferences (Fig. 5). DISCUSS | |
| 73 82 adenosine residue_name The interactions of hADAR2d with base pairs adjacent to the editing site adenosine explain the known 5’ and 3’ nearest neighbor preferences (Fig. 5). DISCUSS | |
| 33 38 ADAR2 protein While these studies indicate the ADAR2 catalytic domain makes an important contact to the 3’ nearest neighbor G, Stefl et al. suggested the 3’ G preference arises from dsRBD binding selectivity for ADAR2. DISCUSS | |
| 39 55 catalytic domain structure_element While these studies indicate the ADAR2 catalytic domain makes an important contact to the 3’ nearest neighbor G, Stefl et al. suggested the 3’ G preference arises from dsRBD binding selectivity for ADAR2. DISCUSS | |
| 110 111 G residue_name While these studies indicate the ADAR2 catalytic domain makes an important contact to the 3’ nearest neighbor G, Stefl et al. suggested the 3’ G preference arises from dsRBD binding selectivity for ADAR2. DISCUSS | |
| 143 144 G residue_name While these studies indicate the ADAR2 catalytic domain makes an important contact to the 3’ nearest neighbor G, Stefl et al. suggested the 3’ G preference arises from dsRBD binding selectivity for ADAR2. DISCUSS | |
| 168 173 dsRBD structure_element While these studies indicate the ADAR2 catalytic domain makes an important contact to the 3’ nearest neighbor G, Stefl et al. suggested the 3’ G preference arises from dsRBD binding selectivity for ADAR2. DISCUSS | |
| 198 203 ADAR2 protein While these studies indicate the ADAR2 catalytic domain makes an important contact to the 3’ nearest neighbor G, Stefl et al. suggested the 3’ G preference arises from dsRBD binding selectivity for ADAR2. DISCUSS | |
| 35 40 ADAR2 protein These authors reported a model for ADAR2’s dsRBDs bound to an editing substrate based on NMR data from the isolated dsRBDs (lacking the deaminase domain) and short RNA fragments derived from the GluR-B R/G site RNA. DISCUSS | |
| 43 49 dsRBDs structure_element These authors reported a model for ADAR2’s dsRBDs bound to an editing substrate based on NMR data from the isolated dsRBDs (lacking the deaminase domain) and short RNA fragments derived from the GluR-B R/G site RNA. DISCUSS | |
| 50 58 bound to protein_state These authors reported a model for ADAR2’s dsRBDs bound to an editing substrate based on NMR data from the isolated dsRBDs (lacking the deaminase domain) and short RNA fragments derived from the GluR-B R/G site RNA. DISCUSS | |
| 89 92 NMR experimental_method These authors reported a model for ADAR2’s dsRBDs bound to an editing substrate based on NMR data from the isolated dsRBDs (lacking the deaminase domain) and short RNA fragments derived from the GluR-B R/G site RNA. DISCUSS | |
| 107 115 isolated protein_state These authors reported a model for ADAR2’s dsRBDs bound to an editing substrate based on NMR data from the isolated dsRBDs (lacking the deaminase domain) and short RNA fragments derived from the GluR-B R/G site RNA. DISCUSS | |
| 116 122 dsRBDs structure_element These authors reported a model for ADAR2’s dsRBDs bound to an editing substrate based on NMR data from the isolated dsRBDs (lacking the deaminase domain) and short RNA fragments derived from the GluR-B R/G site RNA. DISCUSS | |
| 124 131 lacking protein_state These authors reported a model for ADAR2’s dsRBDs bound to an editing substrate based on NMR data from the isolated dsRBDs (lacking the deaminase domain) and short RNA fragments derived from the GluR-B R/G site RNA. DISCUSS | |
| 136 152 deaminase domain structure_element These authors reported a model for ADAR2’s dsRBDs bound to an editing substrate based on NMR data from the isolated dsRBDs (lacking the deaminase domain) and short RNA fragments derived from the GluR-B R/G site RNA. DISCUSS | |
| 164 167 RNA chemical These authors reported a model for ADAR2’s dsRBDs bound to an editing substrate based on NMR data from the isolated dsRBDs (lacking the deaminase domain) and short RNA fragments derived from the GluR-B R/G site RNA. DISCUSS | |
| 195 201 GluR-B protein These authors reported a model for ADAR2’s dsRBDs bound to an editing substrate based on NMR data from the isolated dsRBDs (lacking the deaminase domain) and short RNA fragments derived from the GluR-B R/G site RNA. DISCUSS | |
| 202 210 R/G site site These authors reported a model for ADAR2’s dsRBDs bound to an editing substrate based on NMR data from the isolated dsRBDs (lacking the deaminase domain) and short RNA fragments derived from the GluR-B R/G site RNA. DISCUSS | |
| 211 214 RNA chemical These authors reported a model for ADAR2’s dsRBDs bound to an editing substrate based on NMR data from the isolated dsRBDs (lacking the deaminase domain) and short RNA fragments derived from the GluR-B R/G site RNA. DISCUSS | |
| 44 45 G residue_name They describe an interaction wherein the 3’ G 2-amino group H-bonds to the backbone carbonyl of S258 found in the β1-β2 loop of ADAR2’s dsRBDII. DISCUSS | |
| 60 67 H-bonds bond_interaction They describe an interaction wherein the 3’ G 2-amino group H-bonds to the backbone carbonyl of S258 found in the β1-β2 loop of ADAR2’s dsRBDII. DISCUSS | |
| 96 100 S258 residue_name_number They describe an interaction wherein the 3’ G 2-amino group H-bonds to the backbone carbonyl of S258 found in the β1-β2 loop of ADAR2’s dsRBDII. DISCUSS | |
| 114 124 β1-β2 loop structure_element They describe an interaction wherein the 3’ G 2-amino group H-bonds to the backbone carbonyl of S258 found in the β1-β2 loop of ADAR2’s dsRBDII. DISCUSS | |
| 128 133 ADAR2 protein They describe an interaction wherein the 3’ G 2-amino group H-bonds to the backbone carbonyl of S258 found in the β1-β2 loop of ADAR2’s dsRBDII. DISCUSS | |
| 136 143 dsRBDII structure_element They describe an interaction wherein the 3’ G 2-amino group H-bonds to the backbone carbonyl of S258 found in the β1-β2 loop of ADAR2’s dsRBDII. DISCUSS | |
| 27 31 S486 residue_name_number It is not possible for the S486-3’G interaction we describe here and the S258-3’G interaction reported by Stefl et al. to exist in the same complex since both involve protein loops bound in the RNA minor groove at the same location. DISCUSS | |
| 34 35 G residue_name It is not possible for the S486-3’G interaction we describe here and the S258-3’G interaction reported by Stefl et al. to exist in the same complex since both involve protein loops bound in the RNA minor groove at the same location. DISCUSS | |
| 73 77 S258 residue_name_number It is not possible for the S486-3’G interaction we describe here and the S258-3’G interaction reported by Stefl et al. to exist in the same complex since both involve protein loops bound in the RNA minor groove at the same location. DISCUSS | |
| 80 81 G residue_name It is not possible for the S486-3’G interaction we describe here and the S258-3’G interaction reported by Stefl et al. to exist in the same complex since both involve protein loops bound in the RNA minor groove at the same location. DISCUSS | |
| 181 189 bound in protein_state It is not possible for the S486-3’G interaction we describe here and the S258-3’G interaction reported by Stefl et al. to exist in the same complex since both involve protein loops bound in the RNA minor groove at the same location. DISCUSS | |
| 194 197 RNA chemical It is not possible for the S486-3’G interaction we describe here and the S258-3’G interaction reported by Stefl et al. to exist in the same complex since both involve protein loops bound in the RNA minor groove at the same location. DISCUSS | |
| 198 210 minor groove site It is not possible for the S486-3’G interaction we describe here and the S258-3’G interaction reported by Stefl et al. to exist in the same complex since both involve protein loops bound in the RNA minor groove at the same location. DISCUSS | |
| 12 22 structures evidence Because our structures have captured the edited nucleotide in the conformation required to access the active site, the interactions observed here are highly likely to occur during the deamination reaction at the editing site. DISCUSS | |
| 41 47 edited protein_state Because our structures have captured the edited nucleotide in the conformation required to access the active site, the interactions observed here are highly likely to occur during the deamination reaction at the editing site. DISCUSS | |
| 48 58 nucleotide chemical Because our structures have captured the edited nucleotide in the conformation required to access the active site, the interactions observed here are highly likely to occur during the deamination reaction at the editing site. DISCUSS | |
| 102 113 active site site Because our structures have captured the edited nucleotide in the conformation required to access the active site, the interactions observed here are highly likely to occur during the deamination reaction at the editing site. DISCUSS | |
| 212 224 editing site site Because our structures have captured the edited nucleotide in the conformation required to access the active site, the interactions observed here are highly likely to occur during the deamination reaction at the editing site. DISCUSS | |
| 15 21 dsRBDs structure_element However, since dsRBDs are known to bind promiscuously with duplex RNA, it is possible that the S258-3’G interaction found in a complex lacking the deaminase domain is not relevant to catalysis at the editing site. DISCUSS | |
| 59 69 duplex RNA structure_element However, since dsRBDs are known to bind promiscuously with duplex RNA, it is possible that the S258-3’G interaction found in a complex lacking the deaminase domain is not relevant to catalysis at the editing site. DISCUSS | |
| 95 99 S258 residue_name_number However, since dsRBDs are known to bind promiscuously with duplex RNA, it is possible that the S258-3’G interaction found in a complex lacking the deaminase domain is not relevant to catalysis at the editing site. DISCUSS | |
| 102 103 G residue_name However, since dsRBDs are known to bind promiscuously with duplex RNA, it is possible that the S258-3’G interaction found in a complex lacking the deaminase domain is not relevant to catalysis at the editing site. DISCUSS | |
| 135 146 lacking the protein_state However, since dsRBDs are known to bind promiscuously with duplex RNA, it is possible that the S258-3’G interaction found in a complex lacking the deaminase domain is not relevant to catalysis at the editing site. DISCUSS | |
| 147 163 deaminase domain structure_element However, since dsRBDs are known to bind promiscuously with duplex RNA, it is possible that the S258-3’G interaction found in a complex lacking the deaminase domain is not relevant to catalysis at the editing site. DISCUSS | |
| 200 212 editing site site However, since dsRBDs are known to bind promiscuously with duplex RNA, it is possible that the S258-3’G interaction found in a complex lacking the deaminase domain is not relevant to catalysis at the editing site. DISCUSS | |
| 25 29 ADAR protein_type It is also possible that ADAR dsRBD and catalytic domain binding are sequential, with release of the dsRBD from the RNA taking place prior to catalytic domain engagement and base flipping. DISCUSS | |
| 30 35 dsRBD structure_element It is also possible that ADAR dsRBD and catalytic domain binding are sequential, with release of the dsRBD from the RNA taking place prior to catalytic domain engagement and base flipping. DISCUSS | |
| 40 56 catalytic domain structure_element It is also possible that ADAR dsRBD and catalytic domain binding are sequential, with release of the dsRBD from the RNA taking place prior to catalytic domain engagement and base flipping. DISCUSS | |
| 101 106 dsRBD structure_element It is also possible that ADAR dsRBD and catalytic domain binding are sequential, with release of the dsRBD from the RNA taking place prior to catalytic domain engagement and base flipping. DISCUSS | |
| 116 119 RNA chemical It is also possible that ADAR dsRBD and catalytic domain binding are sequential, with release of the dsRBD from the RNA taking place prior to catalytic domain engagement and base flipping. DISCUSS | |
| 142 158 catalytic domain structure_element It is also possible that ADAR dsRBD and catalytic domain binding are sequential, with release of the dsRBD from the RNA taking place prior to catalytic domain engagement and base flipping. DISCUSS | |
| 85 90 human species Aicardi-Goutieres Syndrome (AGS) and Dyschromatosis Symmetrica Hereditaria (DSH) are human diseases caused by mutations in the human ADAR1 gene and several of the disease-associated mutations are found in the deaminase domain. DISCUSS | |
| 127 132 human species Aicardi-Goutieres Syndrome (AGS) and Dyschromatosis Symmetrica Hereditaria (DSH) are human diseases caused by mutations in the human ADAR1 gene and several of the disease-associated mutations are found in the deaminase domain. DISCUSS | |
| 133 138 ADAR1 protein Aicardi-Goutieres Syndrome (AGS) and Dyschromatosis Symmetrica Hereditaria (DSH) are human diseases caused by mutations in the human ADAR1 gene and several of the disease-associated mutations are found in the deaminase domain. DISCUSS | |
| 209 225 deaminase domain structure_element Aicardi-Goutieres Syndrome (AGS) and Dyschromatosis Symmetrica Hereditaria (DSH) are human diseases caused by mutations in the human ADAR1 gene and several of the disease-associated mutations are found in the deaminase domain. DISCUSS | |
| 26 45 RNA binding surface site Given the conservation in RNA binding surface and active site residues, we expect the hADAR1 catalytic domain to bind RNA with a similar orientation of the helix found in our hADAR2d-RNA structures. DISCUSS | |
| 50 61 active site site Given the conservation in RNA binding surface and active site residues, we expect the hADAR1 catalytic domain to bind RNA with a similar orientation of the helix found in our hADAR2d-RNA structures. DISCUSS | |
| 86 92 hADAR1 protein Given the conservation in RNA binding surface and active site residues, we expect the hADAR1 catalytic domain to bind RNA with a similar orientation of the helix found in our hADAR2d-RNA structures. DISCUSS | |
| 93 109 catalytic domain structure_element Given the conservation in RNA binding surface and active site residues, we expect the hADAR1 catalytic domain to bind RNA with a similar orientation of the helix found in our hADAR2d-RNA structures. DISCUSS | |
| 118 121 RNA chemical Given the conservation in RNA binding surface and active site residues, we expect the hADAR1 catalytic domain to bind RNA with a similar orientation of the helix found in our hADAR2d-RNA structures. DISCUSS | |
| 175 186 hADAR2d-RNA complex_assembly Given the conservation in RNA binding surface and active site residues, we expect the hADAR1 catalytic domain to bind RNA with a similar orientation of the helix found in our hADAR2d-RNA structures. DISCUSS | |
| 187 197 structures evidence Given the conservation in RNA binding surface and active site residues, we expect the hADAR1 catalytic domain to bind RNA with a similar orientation of the helix found in our hADAR2d-RNA structures. DISCUSS | |
| 69 80 hADAR2d-RNA complex_assembly When one maps the locations of the AGS-associated mutations onto the hADAR2d-RNA complex, two mutations involve residues in close proximity to the RNA (< 4 Å) (Supplementary Fig. 8a). DISCUSS | |
| 147 150 RNA chemical When one maps the locations of the AGS-associated mutations onto the hADAR2d-RNA complex, two mutations involve residues in close proximity to the RNA (< 4 Å) (Supplementary Fig. 8a). DISCUSS | |
| 0 4 G487 residue_name_number G487 of hADAR2 is found on the flipping loop near the RNA (Fig. 3b). DISCUSS | |
| 8 14 hADAR2 protein G487 of hADAR2 is found on the flipping loop near the RNA (Fig. 3b). DISCUSS | |
| 31 44 flipping loop structure_element G487 of hADAR2 is found on the flipping loop near the RNA (Fig. 3b). DISCUSS | |
| 54 57 RNA chemical G487 of hADAR2 is found on the flipping loop near the RNA (Fig. 3b). DISCUSS | |
| 17 21 loop structure_element Sequence in this loop is highly conserved among ADARs and corresponds to G1007 in hADAR1 (Supplementary Table 2). DISCUSS | |
| 25 41 highly conserved protein_state Sequence in this loop is highly conserved among ADARs and corresponds to G1007 in hADAR1 (Supplementary Table 2). DISCUSS | |
| 48 53 ADARs protein_type Sequence in this loop is highly conserved among ADARs and corresponds to G1007 in hADAR1 (Supplementary Table 2). DISCUSS | |
| 73 78 G1007 residue_name_number Sequence in this loop is highly conserved among ADARs and corresponds to G1007 in hADAR1 (Supplementary Table 2). DISCUSS | |
| 82 88 hADAR1 protein Sequence in this loop is highly conserved among ADARs and corresponds to G1007 in hADAR1 (Supplementary Table 2). DISCUSS | |
| 3 11 arginine residue_name An arginine at this position would preclude close approach of the flipping loop to the RNA, preventing E1008 insertion and base flipping into the active site (Supplementary Fig. 8b). DISCUSS | |
| 66 79 flipping loop structure_element An arginine at this position would preclude close approach of the flipping loop to the RNA, preventing E1008 insertion and base flipping into the active site (Supplementary Fig. 8b). DISCUSS | |
| 87 90 RNA chemical An arginine at this position would preclude close approach of the flipping loop to the RNA, preventing E1008 insertion and base flipping into the active site (Supplementary Fig. 8b). DISCUSS | |
| 103 108 E1008 residue_name_number An arginine at this position would preclude close approach of the flipping loop to the RNA, preventing E1008 insertion and base flipping into the active site (Supplementary Fig. 8b). DISCUSS | |
| 146 157 active site site An arginine at this position would preclude close approach of the flipping loop to the RNA, preventing E1008 insertion and base flipping into the active site (Supplementary Fig. 8b). DISCUSS | |
| 49 55 G1007R mutant This is consistent with the observation that the G1007R mutation in hADAR1 inhibits RNA editing activity. DISCUSS | |
| 68 74 hADAR1 protein This is consistent with the observation that the G1007R mutation in hADAR1 inhibits RNA editing activity. DISCUSS | |
| 84 87 RNA chemical This is consistent with the observation that the G1007R mutation in hADAR1 inhibits RNA editing activity. DISCUSS | |
| 6 10 K376 residue_name_number Also, K376 forms salt bridges with both the 5’ and 3’ phosphodiesters of the guanosine on the 3’ side of the editing site (Fig. 2). DISCUSS | |
| 17 29 salt bridges bond_interaction Also, K376 forms salt bridges with both the 5’ and 3’ phosphodiesters of the guanosine on the 3’ side of the editing site (Fig. 2). DISCUSS | |
| 77 86 guanosine residue_name Also, K376 forms salt bridges with both the 5’ and 3’ phosphodiesters of the guanosine on the 3’ side of the editing site (Fig. 2). DISCUSS | |
| 109 121 editing site site Also, K376 forms salt bridges with both the 5’ and 3’ phosphodiesters of the guanosine on the 3’ side of the editing site (Fig. 2). DISCUSS | |
| 29 35 hADAR1 protein The corresponding residue in hADAR1 (R892) could form similar contacts and the R892H mutation would likely alter this interaction. DISCUSS | |
| 37 41 R892 residue_name_number The corresponding residue in hADAR1 (R892) could form similar contacts and the R892H mutation would likely alter this interaction. DISCUSS | |
| 79 84 R892H mutant The corresponding residue in hADAR1 (R892) could form similar contacts and the R892H mutation would likely alter this interaction. DISCUSS | |
| 16 26 structures evidence In summary, the structures described here establish human ADAR2 as a base-flipping enzyme that uses a unique mechanism well suited for modifying duplex RNA. DISCUSS | |
| 52 57 human species In summary, the structures described here establish human ADAR2 as a base-flipping enzyme that uses a unique mechanism well suited for modifying duplex RNA. DISCUSS | |
| 58 63 ADAR2 protein In summary, the structures described here establish human ADAR2 as a base-flipping enzyme that uses a unique mechanism well suited for modifying duplex RNA. DISCUSS | |
| 145 155 duplex RNA structure_element In summary, the structures described here establish human ADAR2 as a base-flipping enzyme that uses a unique mechanism well suited for modifying duplex RNA. DISCUSS | |
| 74 78 ADAR protein_type In addition, this work provides a basis for understanding the role of the ADAR catalytic domain in determining editing site selectivity and additional structural context to evaluate the impact of ADAR mutations associated with human disease. DISCUSS | |
| 79 95 catalytic domain structure_element In addition, this work provides a basis for understanding the role of the ADAR catalytic domain in determining editing site selectivity and additional structural context to evaluate the impact of ADAR mutations associated with human disease. DISCUSS | |
| 111 123 editing site site In addition, this work provides a basis for understanding the role of the ADAR catalytic domain in determining editing site selectivity and additional structural context to evaluate the impact of ADAR mutations associated with human disease. DISCUSS | |
| 196 200 ADAR protein_type In addition, this work provides a basis for understanding the role of the ADAR catalytic domain in determining editing site selectivity and additional structural context to evaluate the impact of ADAR mutations associated with human disease. DISCUSS | |
| 227 232 human species In addition, this work provides a basis for understanding the role of the ADAR catalytic domain in determining editing site selectivity and additional structural context to evaluate the impact of ADAR mutations associated with human disease. DISCUSS | |
| 0 5 Human species Human ADAR2 and modified RNAs for crystallography FIG | |
| 6 11 ADAR2 protein Human ADAR2 and modified RNAs for crystallography FIG | |
| 25 29 RNAs chemical Human ADAR2 and modified RNAs for crystallography FIG | |
| 34 49 crystallography experimental_method Human ADAR2 and modified RNAs for crystallography FIG | |
| 18 23 human species a, Domain map for human ADAR2 b, ADAR reaction showing intermediate and 8-azanebularine (N) hydrate that mimics this structure c, Duplex RNAs used for crystallization. FIG | |
| 24 29 ADAR2 protein a, Domain map for human ADAR2 b, ADAR reaction showing intermediate and 8-azanebularine (N) hydrate that mimics this structure c, Duplex RNAs used for crystallization. FIG | |
| 33 37 ADAR protein_type a, Domain map for human ADAR2 b, ADAR reaction showing intermediate and 8-azanebularine (N) hydrate that mimics this structure c, Duplex RNAs used for crystallization. FIG | |
| 72 99 8-azanebularine (N) hydrate chemical a, Domain map for human ADAR2 b, ADAR reaction showing intermediate and 8-azanebularine (N) hydrate that mimics this structure c, Duplex RNAs used for crystallization. FIG | |
| 117 126 structure evidence a, Domain map for human ADAR2 b, ADAR reaction showing intermediate and 8-azanebularine (N) hydrate that mimics this structure c, Duplex RNAs used for crystallization. FIG | |
| 130 141 Duplex RNAs structure_element a, Domain map for human ADAR2 b, ADAR reaction showing intermediate and 8-azanebularine (N) hydrate that mimics this structure c, Duplex RNAs used for crystallization. FIG | |
| 151 166 crystallization experimental_method a, Domain map for human ADAR2 b, ADAR reaction showing intermediate and 8-azanebularine (N) hydrate that mimics this structure c, Duplex RNAs used for crystallization. FIG | |
| 0 11 Bdf2 duplex chemical Bdf2 duplex sequence is derived from an editing site found in S. cerevisiae Bdf2 mRNA and Gli1 duplex has sequence surrounding the human Gli1 mRNA editing site. FIG | |
| 40 52 editing site site Bdf2 duplex sequence is derived from an editing site found in S. cerevisiae Bdf2 mRNA and Gli1 duplex has sequence surrounding the human Gli1 mRNA editing site. FIG | |
| 62 75 S. cerevisiae species Bdf2 duplex sequence is derived from an editing site found in S. cerevisiae Bdf2 mRNA and Gli1 duplex has sequence surrounding the human Gli1 mRNA editing site. FIG | |
| 76 85 Bdf2 mRNA chemical Bdf2 duplex sequence is derived from an editing site found in S. cerevisiae Bdf2 mRNA and Gli1 duplex has sequence surrounding the human Gli1 mRNA editing site. FIG | |
| 90 94 Gli1 protein Bdf2 duplex sequence is derived from an editing site found in S. cerevisiae Bdf2 mRNA and Gli1 duplex has sequence surrounding the human Gli1 mRNA editing site. FIG | |
| 131 136 human species Bdf2 duplex sequence is derived from an editing site found in S. cerevisiae Bdf2 mRNA and Gli1 duplex has sequence surrounding the human Gli1 mRNA editing site. FIG | |
| 137 141 Gli1 protein Bdf2 duplex sequence is derived from an editing site found in S. cerevisiae Bdf2 mRNA and Gli1 duplex has sequence surrounding the human Gli1 mRNA editing site. FIG | |
| 142 146 mRNA chemical Bdf2 duplex sequence is derived from an editing site found in S. cerevisiae Bdf2 mRNA and Gli1 duplex has sequence surrounding the human Gli1 mRNA editing site. FIG | |
| 147 159 editing site site Bdf2 duplex sequence is derived from an editing site found in S. cerevisiae Bdf2 mRNA and Gli1 duplex has sequence surrounding the human Gli1 mRNA editing site. FIG | |
| 0 9 Structure evidence Structure of hADAR2d E488Q bound to the Bdf2-C RNA duplex at 2.75 Å resolution FIG | |
| 13 20 hADAR2d mutant Structure of hADAR2d E488Q bound to the Bdf2-C RNA duplex at 2.75 Å resolution FIG | |
| 21 26 E488Q mutant Structure of hADAR2d E488Q bound to the Bdf2-C RNA duplex at 2.75 Å resolution FIG | |
| 27 35 bound to protein_state Structure of hADAR2d E488Q bound to the Bdf2-C RNA duplex at 2.75 Å resolution FIG | |
| 40 57 Bdf2-C RNA duplex chemical Structure of hADAR2d E488Q bound to the Bdf2-C RNA duplex at 2.75 Å resolution FIG | |
| 42 47 dsRNA chemical a, View of structure perpendicular to the dsRNA helical axis. FIG | |
| 47 58 flipped out protein_state Colors correspond to those in Figs. 1a and 1c; flipped out base N is highlighted red, zinc in grey space-filling sphere, Q488 in yellow, previously disordered aa454–477 loop in green and inositol hexakisphosphate (IHP) in space filling. FIG | |
| 86 90 zinc chemical Colors correspond to those in Figs. 1a and 1c; flipped out base N is highlighted red, zinc in grey space-filling sphere, Q488 in yellow, previously disordered aa454–477 loop in green and inositol hexakisphosphate (IHP) in space filling. FIG | |
| 121 125 Q488 residue_name_number Colors correspond to those in Figs. 1a and 1c; flipped out base N is highlighted red, zinc in grey space-filling sphere, Q488 in yellow, previously disordered aa454–477 loop in green and inositol hexakisphosphate (IHP) in space filling. FIG | |
| 148 158 disordered protein_state Colors correspond to those in Figs. 1a and 1c; flipped out base N is highlighted red, zinc in grey space-filling sphere, Q488 in yellow, previously disordered aa454–477 loop in green and inositol hexakisphosphate (IHP) in space filling. FIG | |
| 161 168 454–477 residue_range Colors correspond to those in Figs. 1a and 1c; flipped out base N is highlighted red, zinc in grey space-filling sphere, Q488 in yellow, previously disordered aa454–477 loop in green and inositol hexakisphosphate (IHP) in space filling. FIG | |
| 169 173 loop structure_element Colors correspond to those in Figs. 1a and 1c; flipped out base N is highlighted red, zinc in grey space-filling sphere, Q488 in yellow, previously disordered aa454–477 loop in green and inositol hexakisphosphate (IHP) in space filling. FIG | |
| 187 212 inositol hexakisphosphate chemical Colors correspond to those in Figs. 1a and 1c; flipped out base N is highlighted red, zinc in grey space-filling sphere, Q488 in yellow, previously disordered aa454–477 loop in green and inositol hexakisphosphate (IHP) in space filling. FIG | |
| 214 217 IHP chemical Colors correspond to those in Figs. 1a and 1c; flipped out base N is highlighted red, zinc in grey space-filling sphere, Q488 in yellow, previously disordered aa454–477 loop in green and inositol hexakisphosphate (IHP) in space filling. FIG | |
| 39 46 hADAR2d mutant A transparent surface is shown for the hADAR2d protein. FIG | |
| 31 36 dsRNA chemical b, View of structure along the dsRNA helical axis. FIG | |
| 35 42 hADAR2d mutant c, Summary of the contacts between hADAR2d E488Q and the Bdf2-C RNA duplex. FIG | |
| 43 48 E488Q mutant c, Summary of the contacts between hADAR2d E488Q and the Bdf2-C RNA duplex. FIG | |
| 57 74 Bdf2-C RNA duplex chemical c, Summary of the contacts between hADAR2d E488Q and the Bdf2-C RNA duplex. FIG | |
| 0 4 ADAR protein_type ADAR recognition of the flipped out and orphaned nucleotides FIG | |
| 24 35 flipped out protein_state ADAR recognition of the flipped out and orphaned nucleotides FIG | |
| 40 48 orphaned protein_state ADAR recognition of the flipped out and orphaned nucleotides FIG | |
| 49 60 nucleotides chemical ADAR recognition of the flipped out and orphaned nucleotides FIG | |
| 19 31 editing site site a, Contacts to the editing site nucleotide (N) in the active site. FIG | |
| 32 42 nucleotide chemical a, Contacts to the editing site nucleotide (N) in the active site. FIG | |
| 54 65 active site site a, Contacts to the editing site nucleotide (N) in the active site. FIG | |
| 3 9 Orphan protein_state b, Orphan nucleotide recognition in the hADAR2d E488Q–Bdf2-C complex. FIG | |
| 10 20 nucleotide chemical b, Orphan nucleotide recognition in the hADAR2d E488Q–Bdf2-C complex. FIG | |
| 40 60 hADAR2d E488Q–Bdf2-C complex_assembly b, Orphan nucleotide recognition in the hADAR2d E488Q–Bdf2-C complex. FIG | |
| 3 9 Orphan protein_state c, Orphan nucleotide recognition in the hADAR2d WT–Bdf2-U complex. FIG | |
| 10 20 nucleotide chemical c, Orphan nucleotide recognition in the hADAR2d WT–Bdf2-U complex. FIG | |
| 40 57 hADAR2d WT–Bdf2-U complex_assembly c, Orphan nucleotide recognition in the hADAR2d WT–Bdf2-U complex. FIG | |
| 6 10 ADAR protein_type Other ADAR-induced changes in RNA conformation FIG | |
| 30 33 RNA chemical Other ADAR-induced changes in RNA conformation FIG | |
| 3 10 hADAR2d mutant a, hADAR2d shifts the position of U11-A13’ base pair from ideal A-form RNA helix (yellow). FIG | |
| 34 37 U11 residue_name_number a, hADAR2d shifts the position of U11-A13’ base pair from ideal A-form RNA helix (yellow). FIG | |
| 38 41 A13 residue_name_number a, hADAR2d shifts the position of U11-A13’ base pair from ideal A-form RNA helix (yellow). FIG | |
| 64 80 A-form RNA helix structure_element a, hADAR2d shifts the position of U11-A13’ base pair from ideal A-form RNA helix (yellow). FIG | |
| 3 10 Overlay experimental_method b, Overlay of Bdf2 duplex RNA and idealized A form duplex of same sequence (yellow) illustrating kink in strand and widening of major groove opposite editing site induced by hADAR2d. FIG | |
| 14 29 Bdf2 duplex RNA chemical b, Overlay of Bdf2 duplex RNA and idealized A form duplex of same sequence (yellow) illustrating kink in strand and widening of major groove opposite editing site induced by hADAR2d. FIG | |
| 44 57 A form duplex structure_element b, Overlay of Bdf2 duplex RNA and idealized A form duplex of same sequence (yellow) illustrating kink in strand and widening of major groove opposite editing site induced by hADAR2d. FIG | |
| 128 140 major groove site b, Overlay of Bdf2 duplex RNA and idealized A form duplex of same sequence (yellow) illustrating kink in strand and widening of major groove opposite editing site induced by hADAR2d. FIG | |
| 150 162 editing site site b, Overlay of Bdf2 duplex RNA and idealized A form duplex of same sequence (yellow) illustrating kink in strand and widening of major groove opposite editing site induced by hADAR2d. FIG | |
| 174 181 hADAR2d mutant b, Overlay of Bdf2 duplex RNA and idealized A form duplex of same sequence (yellow) illustrating kink in strand and widening of major groove opposite editing site induced by hADAR2d. FIG | |
| 20 23 A13 residue_name_number c, Unusual “wobble” A13’-U11 interaction in the hADAR2d WT–Bdf2-U complex shown in stick with H-bond indicated with yellow dashes and distances shown in Å. The position of this base pair in the hADAR2d E488Q–Bdf2-C duplex is shown in wire with H-bonds shown with gray dashes. FIG | |
| 25 28 U11 residue_name_number c, Unusual “wobble” A13’-U11 interaction in the hADAR2d WT–Bdf2-U complex shown in stick with H-bond indicated with yellow dashes and distances shown in Å. The position of this base pair in the hADAR2d E488Q–Bdf2-C duplex is shown in wire with H-bonds shown with gray dashes. FIG | |
| 48 65 hADAR2d WT–Bdf2-U complex_assembly c, Unusual “wobble” A13’-U11 interaction in the hADAR2d WT–Bdf2-U complex shown in stick with H-bond indicated with yellow dashes and distances shown in Å. The position of this base pair in the hADAR2d E488Q–Bdf2-C duplex is shown in wire with H-bonds shown with gray dashes. FIG | |
| 94 100 H-bond bond_interaction c, Unusual “wobble” A13’-U11 interaction in the hADAR2d WT–Bdf2-U complex shown in stick with H-bond indicated with yellow dashes and distances shown in Å. The position of this base pair in the hADAR2d E488Q–Bdf2-C duplex is shown in wire with H-bonds shown with gray dashes. FIG | |
| 194 214 hADAR2d E488Q–Bdf2-C complex_assembly c, Unusual “wobble” A13’-U11 interaction in the hADAR2d WT–Bdf2-U complex shown in stick with H-bond indicated with yellow dashes and distances shown in Å. The position of this base pair in the hADAR2d E488Q–Bdf2-C duplex is shown in wire with H-bonds shown with gray dashes. FIG | |
| 244 251 H-bonds bond_interaction c, Unusual “wobble” A13’-U11 interaction in the hADAR2d WT–Bdf2-U complex shown in stick with H-bond indicated with yellow dashes and distances shown in Å. The position of this base pair in the hADAR2d E488Q–Bdf2-C duplex is shown in wire with H-bonds shown with gray dashes. FIG | |
| 18 30 editing site site Interactions with editing site nearest neighbor nucleotides FIG | |
| 48 59 nucleotides chemical Interactions with editing site nearest neighbor nucleotides FIG | |
| 7 19 minor groove site a, The minor groove edge of the U11-A13’ base pair from the Bdf2 duplex approaches G489; model with a C-G pair at this position suggests a clash with the G 2-amino group b, RNA duplex substrates prepared with different 5’ nearest neighbor nucleotides adjacent to editing site indicated in red (2AP = 2-aminopurine). FIG | |
| 32 35 U11 residue_name_number a, The minor groove edge of the U11-A13’ base pair from the Bdf2 duplex approaches G489; model with a C-G pair at this position suggests a clash with the G 2-amino group b, RNA duplex substrates prepared with different 5’ nearest neighbor nucleotides adjacent to editing site indicated in red (2AP = 2-aminopurine). FIG | |
| 36 39 A13 residue_name_number a, The minor groove edge of the U11-A13’ base pair from the Bdf2 duplex approaches G489; model with a C-G pair at this position suggests a clash with the G 2-amino group b, RNA duplex substrates prepared with different 5’ nearest neighbor nucleotides adjacent to editing site indicated in red (2AP = 2-aminopurine). FIG | |
| 60 71 Bdf2 duplex chemical a, The minor groove edge of the U11-A13’ base pair from the Bdf2 duplex approaches G489; model with a C-G pair at this position suggests a clash with the G 2-amino group b, RNA duplex substrates prepared with different 5’ nearest neighbor nucleotides adjacent to editing site indicated in red (2AP = 2-aminopurine). FIG | |
| 83 87 G489 residue_name_number a, The minor groove edge of the U11-A13’ base pair from the Bdf2 duplex approaches G489; model with a C-G pair at this position suggests a clash with the G 2-amino group b, RNA duplex substrates prepared with different 5’ nearest neighbor nucleotides adjacent to editing site indicated in red (2AP = 2-aminopurine). FIG | |
| 102 110 C-G pair structure_element a, The minor groove edge of the U11-A13’ base pair from the Bdf2 duplex approaches G489; model with a C-G pair at this position suggests a clash with the G 2-amino group b, RNA duplex substrates prepared with different 5’ nearest neighbor nucleotides adjacent to editing site indicated in red (2AP = 2-aminopurine). FIG | |
| 154 155 G residue_name a, The minor groove edge of the U11-A13’ base pair from the Bdf2 duplex approaches G489; model with a C-G pair at this position suggests a clash with the G 2-amino group b, RNA duplex substrates prepared with different 5’ nearest neighbor nucleotides adjacent to editing site indicated in red (2AP = 2-aminopurine). FIG | |
| 173 183 RNA duplex structure_element a, The minor groove edge of the U11-A13’ base pair from the Bdf2 duplex approaches G489; model with a C-G pair at this position suggests a clash with the G 2-amino group b, RNA duplex substrates prepared with different 5’ nearest neighbor nucleotides adjacent to editing site indicated in red (2AP = 2-aminopurine). FIG | |
| 263 275 editing site site a, The minor groove edge of the U11-A13’ base pair from the Bdf2 duplex approaches G489; model with a C-G pair at this position suggests a clash with the G 2-amino group b, RNA duplex substrates prepared with different 5’ nearest neighbor nucleotides adjacent to editing site indicated in red (2AP = 2-aminopurine). FIG | |
| 294 297 2AP structure_element a, The minor groove edge of the U11-A13’ base pair from the Bdf2 duplex approaches G489; model with a C-G pair at this position suggests a clash with the G 2-amino group b, RNA duplex substrates prepared with different 5’ nearest neighbor nucleotides adjacent to editing site indicated in red (2AP = 2-aminopurine). FIG | |
| 300 313 2-aminopurine structure_element a, The minor groove edge of the U11-A13’ base pair from the Bdf2 duplex approaches G489; model with a C-G pair at this position suggests a clash with the G 2-amino group b, RNA duplex substrates prepared with different 5’ nearest neighbor nucleotides adjacent to editing site indicated in red (2AP = 2-aminopurine). FIG | |
| 17 43 deamination rate constants evidence c, Comparison of deamination rate constants by hADAR2d at the editing site adenosine (red) for duplexes bearing different 5’ nearest neighbors; krel = kobs/(kobs for unmodified RNA). FIG | |
| 47 54 hADAR2d mutant c, Comparison of deamination rate constants by hADAR2d at the editing site adenosine (red) for duplexes bearing different 5’ nearest neighbors; krel = kobs/(kobs for unmodified RNA). FIG | |
| 62 74 editing site site c, Comparison of deamination rate constants by hADAR2d at the editing site adenosine (red) for duplexes bearing different 5’ nearest neighbors; krel = kobs/(kobs for unmodified RNA). FIG | |
| 75 84 adenosine residue_name c, Comparison of deamination rate constants by hADAR2d at the editing site adenosine (red) for duplexes bearing different 5’ nearest neighbors; krel = kobs/(kobs for unmodified RNA). FIG | |
| 144 148 krel evidence c, Comparison of deamination rate constants by hADAR2d at the editing site adenosine (red) for duplexes bearing different 5’ nearest neighbors; krel = kobs/(kobs for unmodified RNA). FIG | |
| 151 155 kobs evidence c, Comparison of deamination rate constants by hADAR2d at the editing site adenosine (red) for duplexes bearing different 5’ nearest neighbors; krel = kobs/(kobs for unmodified RNA). FIG | |
| 157 161 kobs evidence c, Comparison of deamination rate constants by hADAR2d at the editing site adenosine (red) for duplexes bearing different 5’ nearest neighbors; krel = kobs/(kobs for unmodified RNA). FIG | |
| 166 176 unmodified protein_state c, Comparison of deamination rate constants by hADAR2d at the editing site adenosine (red) for duplexes bearing different 5’ nearest neighbors; krel = kobs/(kobs for unmodified RNA). FIG | |
| 177 180 RNA chemical c, Comparison of deamination rate constants by hADAR2d at the editing site adenosine (red) for duplexes bearing different 5’ nearest neighbors; krel = kobs/(kobs for unmodified RNA). FIG | |
| 3 9 hADAR2 protein d, hADAR2 S486 backbone H-bond with 3’ G 2-amino group; e, RNA duplex substrates prepared with different 3’ nearest neighbor nucleotides adjacent to editing site indicated in red (I = inosine, N2MeG = N2-methylguanosine, 2AP = 2-aminopurine). FIG | |
| 10 14 S486 residue_name_number d, hADAR2 S486 backbone H-bond with 3’ G 2-amino group; e, RNA duplex substrates prepared with different 3’ nearest neighbor nucleotides adjacent to editing site indicated in red (I = inosine, N2MeG = N2-methylguanosine, 2AP = 2-aminopurine). FIG | |
| 24 30 H-bond bond_interaction d, hADAR2 S486 backbone H-bond with 3’ G 2-amino group; e, RNA duplex substrates prepared with different 3’ nearest neighbor nucleotides adjacent to editing site indicated in red (I = inosine, N2MeG = N2-methylguanosine, 2AP = 2-aminopurine). FIG | |
| 39 40 G residue_name d, hADAR2 S486 backbone H-bond with 3’ G 2-amino group; e, RNA duplex substrates prepared with different 3’ nearest neighbor nucleotides adjacent to editing site indicated in red (I = inosine, N2MeG = N2-methylguanosine, 2AP = 2-aminopurine). FIG | |
| 59 69 RNA duplex structure_element d, hADAR2 S486 backbone H-bond with 3’ G 2-amino group; e, RNA duplex substrates prepared with different 3’ nearest neighbor nucleotides adjacent to editing site indicated in red (I = inosine, N2MeG = N2-methylguanosine, 2AP = 2-aminopurine). FIG | |
| 149 161 editing site site d, hADAR2 S486 backbone H-bond with 3’ G 2-amino group; e, RNA duplex substrates prepared with different 3’ nearest neighbor nucleotides adjacent to editing site indicated in red (I = inosine, N2MeG = N2-methylguanosine, 2AP = 2-aminopurine). FIG | |
| 180 181 I residue_name d, hADAR2 S486 backbone H-bond with 3’ G 2-amino group; e, RNA duplex substrates prepared with different 3’ nearest neighbor nucleotides adjacent to editing site indicated in red (I = inosine, N2MeG = N2-methylguanosine, 2AP = 2-aminopurine). FIG | |
| 184 191 inosine residue_name d, hADAR2 S486 backbone H-bond with 3’ G 2-amino group; e, RNA duplex substrates prepared with different 3’ nearest neighbor nucleotides adjacent to editing site indicated in red (I = inosine, N2MeG = N2-methylguanosine, 2AP = 2-aminopurine). FIG | |
| 221 224 2AP structure_element d, hADAR2 S486 backbone H-bond with 3’ G 2-amino group; e, RNA duplex substrates prepared with different 3’ nearest neighbor nucleotides adjacent to editing site indicated in red (I = inosine, N2MeG = N2-methylguanosine, 2AP = 2-aminopurine). FIG | |
| 227 240 2-aminopurine structure_element d, hADAR2 S486 backbone H-bond with 3’ G 2-amino group; e, RNA duplex substrates prepared with different 3’ nearest neighbor nucleotides adjacent to editing site indicated in red (I = inosine, N2MeG = N2-methylguanosine, 2AP = 2-aminopurine). FIG | |
| 17 43 deamination rate constants evidence f, Comparison of deamination rate constants by hADAR2d at the editing site adenosine (red) for duplexes bearing different 3’ nearest neighbors. FIG | |
| 47 54 hADAR2d mutant f, Comparison of deamination rate constants by hADAR2d at the editing site adenosine (red) for duplexes bearing different 3’ nearest neighbors. FIG | |
| 62 74 editing site site f, Comparison of deamination rate constants by hADAR2d at the editing site adenosine (red) for duplexes bearing different 3’ nearest neighbors. FIG | |
| 75 84 adenosine residue_name f, Comparison of deamination rate constants by hADAR2d at the editing site adenosine (red) for duplexes bearing different 3’ nearest neighbors. FIG | |
| 0 4 krel evidence krel = kobs/(kobs for unmodified RNA). FIG | |
| 7 11 kobs evidence krel = kobs/(kobs for unmodified RNA). FIG | |
| 13 17 kobs evidence krel = kobs/(kobs for unmodified RNA). FIG | |
| 22 32 unmodified protein_state krel = kobs/(kobs for unmodified RNA). FIG | |
| 33 36 RNA chemical krel = kobs/(kobs for unmodified RNA). FIG | |
| 0 17 RNA-binding loops structure_element RNA-binding loops in the ADAR catalytic domain FIG | |
| 25 29 ADAR protein_type RNA-binding loops in the ADAR catalytic domain FIG | |
| 30 46 catalytic domain structure_element RNA-binding loops in the ADAR catalytic domain FIG | |
| 3 9 hADAR2 protein a, hADAR2 residues that contact phosphodiester backbone near 5’ end of unedited strand. FIG | |
| 39 60 protein-RNA interface site b, Location of mutations introduced at protein-RNA interface. FIG | |
| 17 43 deamination rate constants evidence c, Comparison of deamination rate constants of the different hADAR2d mutants (Log scale). FIG | |
| 61 68 hADAR2d mutant c, Comparison of deamination rate constants of the different hADAR2d mutants (Log scale). FIG | |
| 0 4 krel evidence krel = kobs for mutant/kobs for WT. FIG | |
| 7 11 kobs evidence krel = kobs for mutant/kobs for WT. FIG | |
| 16 22 mutant protein_state krel = kobs for mutant/kobs for WT. FIG | |
| 23 27 kobs evidence krel = kobs for mutant/kobs for WT. FIG | |
| 32 34 WT protein_state krel = kobs for mutant/kobs for WT. FIG | |
| 3 21 Sequence alignment experimental_method d, Sequence alignment of ADAR2s (A2) and ADAR1s (A1) from different organisms with different levels of conservation colored (Yellow: conserved in all ADAR1s and ADAR2s, red: conserved in ADAR2s, blue: conserved in ADAR1s. FIG | |
| 25 31 ADAR2s protein_type d, Sequence alignment of ADAR2s (A2) and ADAR1s (A1) from different organisms with different levels of conservation colored (Yellow: conserved in all ADAR1s and ADAR2s, red: conserved in ADAR2s, blue: conserved in ADAR1s. FIG | |
| 41 47 ADAR1s protein_type d, Sequence alignment of ADAR2s (A2) and ADAR1s (A1) from different organisms with different levels of conservation colored (Yellow: conserved in all ADAR1s and ADAR2s, red: conserved in ADAR2s, blue: conserved in ADAR1s. FIG | |
| 133 142 conserved protein_state d, Sequence alignment of ADAR2s (A2) and ADAR1s (A1) from different organisms with different levels of conservation colored (Yellow: conserved in all ADAR1s and ADAR2s, red: conserved in ADAR2s, blue: conserved in ADAR1s. FIG | |
| 150 156 ADAR1s protein_type d, Sequence alignment of ADAR2s (A2) and ADAR1s (A1) from different organisms with different levels of conservation colored (Yellow: conserved in all ADAR1s and ADAR2s, red: conserved in ADAR2s, blue: conserved in ADAR1s. FIG | |
| 161 167 ADAR2s protein_type d, Sequence alignment of ADAR2s (A2) and ADAR1s (A1) from different organisms with different levels of conservation colored (Yellow: conserved in all ADAR1s and ADAR2s, red: conserved in ADAR2s, blue: conserved in ADAR1s. FIG | |
| 174 183 conserved protein_state d, Sequence alignment of ADAR2s (A2) and ADAR1s (A1) from different organisms with different levels of conservation colored (Yellow: conserved in all ADAR1s and ADAR2s, red: conserved in ADAR2s, blue: conserved in ADAR1s. FIG | |
| 187 193 ADAR2s protein_type d, Sequence alignment of ADAR2s (A2) and ADAR1s (A1) from different organisms with different levels of conservation colored (Yellow: conserved in all ADAR1s and ADAR2s, red: conserved in ADAR2s, blue: conserved in ADAR1s. FIG | |
| 201 210 conserved protein_state d, Sequence alignment of ADAR2s (A2) and ADAR1s (A1) from different organisms with different levels of conservation colored (Yellow: conserved in all ADAR1s and ADAR2s, red: conserved in ADAR2s, blue: conserved in ADAR1s. FIG | |
| 214 220 ADAR1s protein_type d, Sequence alignment of ADAR2s (A2) and ADAR1s (A1) from different organisms with different levels of conservation colored (Yellow: conserved in all ADAR1s and ADAR2s, red: conserved in ADAR2s, blue: conserved in ADAR1s. FIG | |
| 22 52 ADAR-specific RNA-binding loop structure_element e, Interaction of the ADAR-specific RNA-binding loop near the 5’ end of the edited strand. FIG | |
| 23 36 not conserved protein_state Colors as in d, white: not conserved, flipped out base is shown in pink. FIG | |
| 38 49 flipped out protein_state Colors as in d, white: not conserved, flipped out base is shown in pink. FIG | |
| 50 54 base chemical Colors as in d, white: not conserved, flipped out base is shown in pink. FIG | |