annotation_CSV/PMC4918759.csv

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