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0 17 Crystal Structure evidence Crystal Structure and Activity Studies of the C11 Cysteine Peptidase from Parabacteroides merdae in the Human Gut Microbiome* TITLE
22 38 Activity Studies experimental_method Crystal Structure and Activity Studies of the C11 Cysteine Peptidase from Parabacteroides merdae in the Human Gut Microbiome* TITLE
46 49 C11 protein_type Crystal Structure and Activity Studies of the C11 Cysteine Peptidase from Parabacteroides merdae in the Human Gut Microbiome* TITLE
50 68 Cysteine Peptidase protein_type Crystal Structure and Activity Studies of the C11 Cysteine Peptidase from Parabacteroides merdae in the Human Gut Microbiome* TITLE
74 96 Parabacteroides merdae species Crystal Structure and Activity Studies of the C11 Cysteine Peptidase from Parabacteroides merdae in the Human Gut Microbiome* TITLE
104 109 Human species Crystal Structure and Activity Studies of the C11 Cysteine Peptidase from Parabacteroides merdae in the Human Gut Microbiome* TITLE
0 27 Clan CD cysteine peptidases protein_type Clan CD cysteine peptidases, a structurally related group of peptidases that include mammalian caspases, exhibit a wide range of important functions, along with a variety of specificities and activation mechanisms. ABSTRACT
61 71 peptidases protein_type Clan CD cysteine peptidases, a structurally related group of peptidases that include mammalian caspases, exhibit a wide range of important functions, along with a variety of specificities and activation mechanisms. ABSTRACT
85 94 mammalian taxonomy_domain Clan CD cysteine peptidases, a structurally related group of peptidases that include mammalian caspases, exhibit a wide range of important functions, along with a variety of specificities and activation mechanisms. ABSTRACT
95 103 caspases protein_type Clan CD cysteine peptidases, a structurally related group of peptidases that include mammalian caspases, exhibit a wide range of important functions, along with a variety of specificities and activation mechanisms. ABSTRACT
17 35 clostripain family protein_type However, for the clostripain family (denoted C11), little is currently known. ABSTRACT
45 48 C11 protein_type However, for the clostripain family (denoted C11), little is currently known. ABSTRACT
28 45 crystal structure evidence Here, we describe the first crystal structure of a C11 protein from the human gut bacterium, Parabacteroides merdae (PmC11), determined to 1.7-Å resolution. ABSTRACT
51 54 C11 protein_type Here, we describe the first crystal structure of a C11 protein from the human gut bacterium, Parabacteroides merdae (PmC11), determined to 1.7-Å resolution. ABSTRACT
72 77 human species Here, we describe the first crystal structure of a C11 protein from the human gut bacterium, Parabacteroides merdae (PmC11), determined to 1.7-Å resolution. ABSTRACT
82 91 bacterium taxonomy_domain Here, we describe the first crystal structure of a C11 protein from the human gut bacterium, Parabacteroides merdae (PmC11), determined to 1.7-Å resolution. ABSTRACT
93 115 Parabacteroides merdae species Here, we describe the first crystal structure of a C11 protein from the human gut bacterium, Parabacteroides merdae (PmC11), determined to 1.7-Å resolution. ABSTRACT
117 122 PmC11 protein Here, we describe the first crystal structure of a C11 protein from the human gut bacterium, Parabacteroides merdae (PmC11), determined to 1.7-Å resolution. ABSTRACT
0 5 PmC11 protein PmC11 is a monomeric cysteine peptidase that comprises an extended caspase-like α/β/α sandwich and an unusual C-terminal domain. ABSTRACT
11 20 monomeric oligomeric_state PmC11 is a monomeric cysteine peptidase that comprises an extended caspase-like α/β/α sandwich and an unusual C-terminal domain. ABSTRACT
21 39 cysteine peptidase protein_type PmC11 is a monomeric cysteine peptidase that comprises an extended caspase-like α/β/α sandwich and an unusual C-terminal domain. ABSTRACT
58 94 extended caspase-like α/β/α sandwich structure_element PmC11 is a monomeric cysteine peptidase that comprises an extended caspase-like α/β/α sandwich and an unusual C-terminal domain. ABSTRACT
110 127 C-terminal domain structure_element PmC11 is a monomeric cysteine peptidase that comprises an extended caspase-like α/β/α sandwich and an unusual C-terminal domain. ABSTRACT
40 67 clan CD cysteine peptidases protein_type It shares core structural elements with clan CD cysteine peptidases but otherwise structurally differs from the other families in the clan. ABSTRACT
77 83 Lys147 residue_name_number These studies also revealed a well ordered break in the polypeptide chain at Lys147, resulting in a large conformational rearrangement close to the active site. ABSTRACT
148 159 active site site These studies also revealed a well ordered break in the polypeptide chain at Lys147, resulting in a large conformational rearrangement close to the active site. ABSTRACT
0 32 Biochemical and kinetic analysis experimental_method Biochemical and kinetic analysis revealed Lys147 to be an intramolecular processing site at which cleavage is required for full activation of the enzyme, suggesting an autoinhibitory mechanism for self-preservation. ABSTRACT
42 48 Lys147 residue_name_number Biochemical and kinetic analysis revealed Lys147 to be an intramolecular processing site at which cleavage is required for full activation of the enzyme, suggesting an autoinhibitory mechanism for self-preservation. ABSTRACT
58 88 intramolecular processing site site Biochemical and kinetic analysis revealed Lys147 to be an intramolecular processing site at which cleavage is required for full activation of the enzyme, suggesting an autoinhibitory mechanism for self-preservation. ABSTRACT
98 106 cleavage ptm Biochemical and kinetic analysis revealed Lys147 to be an intramolecular processing site at which cleavage is required for full activation of the enzyme, suggesting an autoinhibitory mechanism for self-preservation. ABSTRACT
123 138 full activation protein_state Biochemical and kinetic analysis revealed Lys147 to be an intramolecular processing site at which cleavage is required for full activation of the enzyme, suggesting an autoinhibitory mechanism for self-preservation. ABSTRACT
146 152 enzyme protein Biochemical and kinetic analysis revealed Lys147 to be an intramolecular processing site at which cleavage is required for full activation of the enzyme, suggesting an autoinhibitory mechanism for self-preservation. ABSTRACT
0 5 PmC11 protein PmC11 has an acidic binding pocket and a preference for basic substrates, and accepts substrates with Arg and Lys in P1 and does not require Ca2+ for activity. ABSTRACT
13 34 acidic binding pocket site PmC11 has an acidic binding pocket and a preference for basic substrates, and accepts substrates with Arg and Lys in P1 and does not require Ca2+ for activity. ABSTRACT
102 105 Arg residue_name PmC11 has an acidic binding pocket and a preference for basic substrates, and accepts substrates with Arg and Lys in P1 and does not require Ca2+ for activity. ABSTRACT
110 113 Lys residue_name PmC11 has an acidic binding pocket and a preference for basic substrates, and accepts substrates with Arg and Lys in P1 and does not require Ca2+ for activity. ABSTRACT
117 119 P1 residue_number PmC11 has an acidic binding pocket and a preference for basic substrates, and accepts substrates with Arg and Lys in P1 and does not require Ca2+ for activity. ABSTRACT
141 145 Ca2+ chemical PmC11 has an acidic binding pocket and a preference for basic substrates, and accepts substrates with Arg and Lys in P1 and does not require Ca2+ for activity. ABSTRACT
77 82 PmC11 protein Collectively, these data provide insights into the mechanism and activity of PmC11 and a detailed framework for studies on C11 peptidases from other phylogenetic kingdoms. ABSTRACT
123 137 C11 peptidases protein_type Collectively, these data provide insights into the mechanism and activity of PmC11 and a detailed framework for studies on C11 peptidases from other phylogenetic kingdoms. ABSTRACT
0 19 Cysteine peptidases protein_type Cysteine peptidases play crucial roles in the virulence of bacterial and other eukaryotic pathogens. INTRO
59 68 bacterial taxonomy_domain Cysteine peptidases play crucial roles in the virulence of bacterial and other eukaryotic pathogens. INTRO
79 89 eukaryotic taxonomy_domain Cysteine peptidases play crucial roles in the virulence of bacterial and other eukaryotic pathogens. INTRO
34 41 clan CD protein_type In the MEROPS peptidase database, clan CD contains groups (or families) of cysteine peptidases that share some highly conserved structural elements. INTRO
75 94 cysteine peptidases protein_type In the MEROPS peptidase database, clan CD contains groups (or families) of cysteine peptidases that share some highly conserved structural elements. INTRO
111 127 highly conserved protein_state In the MEROPS peptidase database, clan CD contains groups (or families) of cysteine peptidases that share some highly conserved structural elements. INTRO
0 16 Clan CD families protein_type Clan CD families are typically described using the name of their archetypal, or founding, member and also given an identification number preceded by a “C,” to denote cysteine peptidase. INTRO
166 184 cysteine peptidase protein_type Clan CD families are typically described using the name of their archetypal, or founding, member and also given an identification number preceded by a “C,” to denote cysteine peptidase. INTRO
110 128 crystal structures evidence Although seven families (C14 is additionally split into three subfamilies) have been described for this clan, crystal structures have only been determined from four: legumain (C13), caspase (C14a), paracaspase (C14b(P), metacaspase (C14b(M), gingipain (C25), and the cysteine peptidase domain (CPD) of various toxins (C80). INTRO
166 174 legumain protein Although seven families (C14 is additionally split into three subfamilies) have been described for this clan, crystal structures have only been determined from four: legumain (C13), caspase (C14a), paracaspase (C14b(P), metacaspase (C14b(M), gingipain (C25), and the cysteine peptidase domain (CPD) of various toxins (C80). INTRO
176 179 C13 protein_type Although seven families (C14 is additionally split into three subfamilies) have been described for this clan, crystal structures have only been determined from four: legumain (C13), caspase (C14a), paracaspase (C14b(P), metacaspase (C14b(M), gingipain (C25), and the cysteine peptidase domain (CPD) of various toxins (C80). INTRO
182 189 caspase protein Although seven families (C14 is additionally split into three subfamilies) have been described for this clan, crystal structures have only been determined from four: legumain (C13), caspase (C14a), paracaspase (C14b(P), metacaspase (C14b(M), gingipain (C25), and the cysteine peptidase domain (CPD) of various toxins (C80). INTRO
191 195 C14a protein_type Although seven families (C14 is additionally split into three subfamilies) have been described for this clan, crystal structures have only been determined from four: legumain (C13), caspase (C14a), paracaspase (C14b(P), metacaspase (C14b(M), gingipain (C25), and the cysteine peptidase domain (CPD) of various toxins (C80). INTRO
198 209 paracaspase protein Although seven families (C14 is additionally split into three subfamilies) have been described for this clan, crystal structures have only been determined from four: legumain (C13), caspase (C14a), paracaspase (C14b(P), metacaspase (C14b(M), gingipain (C25), and the cysteine peptidase domain (CPD) of various toxins (C80). INTRO
211 217 C14b(P protein_type Although seven families (C14 is additionally split into three subfamilies) have been described for this clan, crystal structures have only been determined from four: legumain (C13), caspase (C14a), paracaspase (C14b(P), metacaspase (C14b(M), gingipain (C25), and the cysteine peptidase domain (CPD) of various toxins (C80). INTRO
220 231 metacaspase protein Although seven families (C14 is additionally split into three subfamilies) have been described for this clan, crystal structures have only been determined from four: legumain (C13), caspase (C14a), paracaspase (C14b(P), metacaspase (C14b(M), gingipain (C25), and the cysteine peptidase domain (CPD) of various toxins (C80). INTRO
233 239 C14b(M protein_type Although seven families (C14 is additionally split into three subfamilies) have been described for this clan, crystal structures have only been determined from four: legumain (C13), caspase (C14a), paracaspase (C14b(P), metacaspase (C14b(M), gingipain (C25), and the cysteine peptidase domain (CPD) of various toxins (C80). INTRO
242 251 gingipain protein Although seven families (C14 is additionally split into three subfamilies) have been described for this clan, crystal structures have only been determined from four: legumain (C13), caspase (C14a), paracaspase (C14b(P), metacaspase (C14b(M), gingipain (C25), and the cysteine peptidase domain (CPD) of various toxins (C80). INTRO
253 256 C25 protein_type Although seven families (C14 is additionally split into three subfamilies) have been described for this clan, crystal structures have only been determined from four: legumain (C13), caspase (C14a), paracaspase (C14b(P), metacaspase (C14b(M), gingipain (C25), and the cysteine peptidase domain (CPD) of various toxins (C80). INTRO
267 292 cysteine peptidase domain structure_element Although seven families (C14 is additionally split into three subfamilies) have been described for this clan, crystal structures have only been determined from four: legumain (C13), caspase (C14a), paracaspase (C14b(P), metacaspase (C14b(M), gingipain (C25), and the cysteine peptidase domain (CPD) of various toxins (C80). INTRO
294 297 CPD structure_element Although seven families (C14 is additionally split into three subfamilies) have been described for this clan, crystal structures have only been determined from four: legumain (C13), caspase (C14a), paracaspase (C14b(P), metacaspase (C14b(M), gingipain (C25), and the cysteine peptidase domain (CPD) of various toxins (C80). INTRO
318 321 C80 protein_type Although seven families (C14 is additionally split into three subfamilies) have been described for this clan, crystal structures have only been determined from four: legumain (C13), caspase (C14a), paracaspase (C14b(P), metacaspase (C14b(M), gingipain (C25), and the cysteine peptidase domain (CPD) of various toxins (C80). INTRO
43 54 clostripain protein No structural information is available for clostripain (C11), separase (C50), or PrtH-peptidase (C85). INTRO
56 59 C11 protein_type No structural information is available for clostripain (C11), separase (C50), or PrtH-peptidase (C85). INTRO
62 70 separase protein No structural information is available for clostripain (C11), separase (C50), or PrtH-peptidase (C85). INTRO
72 75 C50 protein_type No structural information is available for clostripain (C11), separase (C50), or PrtH-peptidase (C85). INTRO
81 95 PrtH-peptidase protein No structural information is available for clostripain (C11), separase (C50), or PrtH-peptidase (C85). INTRO
97 100 C85 protein_type No structural information is available for clostripain (C11), separase (C50), or PrtH-peptidase (C85). INTRO
0 15 Clan CD enzymes protein_type Clan CD enzymes have a highly conserved His/Cys catalytic dyad and exhibit strict specificity for the P1 residue of their substrates. INTRO
23 39 highly conserved protein_state Clan CD enzymes have a highly conserved His/Cys catalytic dyad and exhibit strict specificity for the P1 residue of their substrates. INTRO
40 62 His/Cys catalytic dyad site Clan CD enzymes have a highly conserved His/Cys catalytic dyad and exhibit strict specificity for the P1 residue of their substrates. INTRO
102 104 P1 residue_number Clan CD enzymes have a highly conserved His/Cys catalytic dyad and exhibit strict specificity for the P1 residue of their substrates. INTRO
37 44 clan CD protein_type However, despite these similarities, clan CD forms a functionally diverse group of enzymes: the overall structural diversity between (and at times within) the various families provides these peptidases with a wide variety of substrate specificities and activation mechanisms. INTRO
191 201 peptidases protein_type However, despite these similarities, clan CD forms a functionally diverse group of enzymes: the overall structural diversity between (and at times within) the various families provides these peptidases with a wide variety of substrate specificities and activation mechanisms. INTRO
75 84 mammalian taxonomy_domain The archetypal and arguably most notable family in the clan is that of the mammalian caspases (C14a), although clan CD members are distributed throughout the entire phylogenetic kingdom and are often required in fundamental biological processes. INTRO
85 93 caspases protein_type The archetypal and arguably most notable family in the clan is that of the mammalian caspases (C14a), although clan CD members are distributed throughout the entire phylogenetic kingdom and are often required in fundamental biological processes. INTRO
95 99 C14a protein_type The archetypal and arguably most notable family in the clan is that of the mammalian caspases (C14a), although clan CD members are distributed throughout the entire phylogenetic kingdom and are often required in fundamental biological processes. INTRO
111 118 clan CD protein_type The archetypal and arguably most notable family in the clan is that of the mammalian caspases (C14a), although clan CD members are distributed throughout the entire phylogenetic kingdom and are often required in fundamental biological processes. INTRO
70 73 C11 protein_type Interestingly, little is known about the structure or function of the C11 proteins, despite their widespread distribution and its archetypal member, clostripain from Clostridium histolyticum, first reported in the literature in 1938. INTRO
149 160 clostripain protein Interestingly, little is known about the structure or function of the C11 proteins, despite their widespread distribution and its archetypal member, clostripain from Clostridium histolyticum, first reported in the literature in 1938. INTRO
166 190 Clostridium histolyticum species Interestingly, little is known about the structure or function of the C11 proteins, despite their widespread distribution and its archetypal member, clostripain from Clostridium histolyticum, first reported in the literature in 1938. INTRO
0 11 Clostripain protein Clostripain has been described as an arginine-specific peptidase with a requirement for Ca2+ and loss of an internal nonapeptide for full activation; lack of structural information on the family appears to have prohibited further investigation. INTRO
37 64 arginine-specific peptidase protein_type Clostripain has been described as an arginine-specific peptidase with a requirement for Ca2+ and loss of an internal nonapeptide for full activation; lack of structural information on the family appears to have prohibited further investigation. INTRO
88 92 Ca2+ chemical Clostripain has been described as an arginine-specific peptidase with a requirement for Ca2+ and loss of an internal nonapeptide for full activation; lack of structural information on the family appears to have prohibited further investigation. INTRO
108 128 internal nonapeptide structure_element Clostripain has been described as an arginine-specific peptidase with a requirement for Ca2+ and loss of an internal nonapeptide for full activation; lack of structural information on the family appears to have prohibited further investigation. INTRO
133 148 full activation protein_state Clostripain has been described as an arginine-specific peptidase with a requirement for Ca2+ and loss of an internal nonapeptide for full activation; lack of structural information on the family appears to have prohibited further investigation. INTRO
56 64 bacteria taxonomy_domain As part of an ongoing project to characterize commensal bacteria in the microbiome that inhabit the human gut, the structure of C11 peptidase, PmC11, from Parabacteroides merdae was determined using the Joint Center for Structural Genomics (JCSG)4 HTP structural biology pipeline. INTRO
100 105 human species As part of an ongoing project to characterize commensal bacteria in the microbiome that inhabit the human gut, the structure of C11 peptidase, PmC11, from Parabacteroides merdae was determined using the Joint Center for Structural Genomics (JCSG)4 HTP structural biology pipeline. INTRO
115 124 structure evidence As part of an ongoing project to characterize commensal bacteria in the microbiome that inhabit the human gut, the structure of C11 peptidase, PmC11, from Parabacteroides merdae was determined using the Joint Center for Structural Genomics (JCSG)4 HTP structural biology pipeline. INTRO
128 141 C11 peptidase protein_type As part of an ongoing project to characterize commensal bacteria in the microbiome that inhabit the human gut, the structure of C11 peptidase, PmC11, from Parabacteroides merdae was determined using the Joint Center for Structural Genomics (JCSG)4 HTP structural biology pipeline. INTRO
143 148 PmC11 protein As part of an ongoing project to characterize commensal bacteria in the microbiome that inhabit the human gut, the structure of C11 peptidase, PmC11, from Parabacteroides merdae was determined using the Joint Center for Structural Genomics (JCSG)4 HTP structural biology pipeline. INTRO
155 177 Parabacteroides merdae species As part of an ongoing project to characterize commensal bacteria in the microbiome that inhabit the human gut, the structure of C11 peptidase, PmC11, from Parabacteroides merdae was determined using the Joint Center for Structural Genomics (JCSG)4 HTP structural biology pipeline. INTRO
4 26 structure was analyzed experimental_method The structure was analyzed, and the enzyme was biochemically characterized to provide the first structure/function correlation for a C11 peptidase. INTRO
47 74 biochemically characterized experimental_method The structure was analyzed, and the enzyme was biochemically characterized to provide the first structure/function correlation for a C11 peptidase. INTRO
133 146 C11 peptidase protein_type The structure was analyzed, and the enzyme was biochemically characterized to provide the first structure/function correlation for a C11 peptidase. INTRO
0 9 Structure evidence Structure of PmC11 RESULTS
13 18 PmC11 protein Structure of PmC11 RESULTS
4 21 crystal structure evidence The crystal structure of the catalytically active form of PmC11 revealed an extended caspase-like α/β/α sandwich architecture comprised of a central nine-stranded β-sheet, with an unusual C-terminal domain (CTD), starting at Lys250. RESULTS
29 49 catalytically active protein_state The crystal structure of the catalytically active form of PmC11 revealed an extended caspase-like α/β/α sandwich architecture comprised of a central nine-stranded β-sheet, with an unusual C-terminal domain (CTD), starting at Lys250. RESULTS
58 63 PmC11 protein The crystal structure of the catalytically active form of PmC11 revealed an extended caspase-like α/β/α sandwich architecture comprised of a central nine-stranded β-sheet, with an unusual C-terminal domain (CTD), starting at Lys250. RESULTS
76 112 extended caspase-like α/β/α sandwich structure_element The crystal structure of the catalytically active form of PmC11 revealed an extended caspase-like α/β/α sandwich architecture comprised of a central nine-stranded β-sheet, with an unusual C-terminal domain (CTD), starting at Lys250. RESULTS
149 170 nine-stranded β-sheet structure_element The crystal structure of the catalytically active form of PmC11 revealed an extended caspase-like α/β/α sandwich architecture comprised of a central nine-stranded β-sheet, with an unusual C-terminal domain (CTD), starting at Lys250. RESULTS
188 205 C-terminal domain structure_element The crystal structure of the catalytically active form of PmC11 revealed an extended caspase-like α/β/α sandwich architecture comprised of a central nine-stranded β-sheet, with an unusual C-terminal domain (CTD), starting at Lys250. RESULTS
207 210 CTD structure_element The crystal structure of the catalytically active form of PmC11 revealed an extended caspase-like α/β/α sandwich architecture comprised of a central nine-stranded β-sheet, with an unusual C-terminal domain (CTD), starting at Lys250. RESULTS
225 231 Lys250 residue_name_number The crystal structure of the catalytically active form of PmC11 revealed an extended caspase-like α/β/α sandwich architecture comprised of a central nine-stranded β-sheet, with an unusual C-terminal domain (CTD), starting at Lys250. RESULTS
2 17 single cleavage ptm A single cleavage was observed in the polypeptide chain at Lys147 (Fig. 1, A and B), where both ends of the cleavage site are fully visible and well ordered in the electron density. RESULTS
59 65 Lys147 residue_name_number A single cleavage was observed in the polypeptide chain at Lys147 (Fig. 1, A and B), where both ends of the cleavage site are fully visible and well ordered in the electron density. RESULTS
108 121 cleavage site site A single cleavage was observed in the polypeptide chain at Lys147 (Fig. 1, A and B), where both ends of the cleavage site are fully visible and well ordered in the electron density. RESULTS
164 180 electron density evidence A single cleavage was observed in the polypeptide chain at Lys147 (Fig. 1, A and B), where both ends of the cleavage site are fully visible and well ordered in the electron density. RESULTS
12 33 nine-stranded β-sheet structure_element The central nine-stranded β-sheet (β1–β9) of PmC11 consists of six parallel and three anti-parallel β-strands with 4↑3↓2↑1↑5↑6↑7↓8↓9↑ topology (Fig. 1A) and the overall structure includes 14 α-helices with six (α1–α2 and α4–α7) closely surrounding the β-sheet in an approximately parallel orientation. RESULTS
35 40 β1–β9 structure_element The central nine-stranded β-sheet (β1–β9) of PmC11 consists of six parallel and three anti-parallel β-strands with 4↑3↓2↑1↑5↑6↑7↓8↓9↑ topology (Fig. 1A) and the overall structure includes 14 α-helices with six (α1–α2 and α4–α7) closely surrounding the β-sheet in an approximately parallel orientation. RESULTS
45 50 PmC11 protein The central nine-stranded β-sheet (β1–β9) of PmC11 consists of six parallel and three anti-parallel β-strands with 4↑3↓2↑1↑5↑6↑7↓8↓9↑ topology (Fig. 1A) and the overall structure includes 14 α-helices with six (α1–α2 and α4–α7) closely surrounding the β-sheet in an approximately parallel orientation. RESULTS
67 75 parallel structure_element The central nine-stranded β-sheet (β1–β9) of PmC11 consists of six parallel and three anti-parallel β-strands with 4↑3↓2↑1↑5↑6↑7↓8↓9↑ topology (Fig. 1A) and the overall structure includes 14 α-helices with six (α1–α2 and α4–α7) closely surrounding the β-sheet in an approximately parallel orientation. RESULTS
86 109 anti-parallel β-strands structure_element The central nine-stranded β-sheet (β1–β9) of PmC11 consists of six parallel and three anti-parallel β-strands with 4↑3↓2↑1↑5↑6↑7↓8↓9↑ topology (Fig. 1A) and the overall structure includes 14 α-helices with six (α1–α2 and α4–α7) closely surrounding the β-sheet in an approximately parallel orientation. RESULTS
169 178 structure evidence The central nine-stranded β-sheet (β1–β9) of PmC11 consists of six parallel and three anti-parallel β-strands with 4↑3↓2↑1↑5↑6↑7↓8↓9↑ topology (Fig. 1A) and the overall structure includes 14 α-helices with six (α1–α2 and α4–α7) closely surrounding the β-sheet in an approximately parallel orientation. RESULTS
191 200 α-helices structure_element The central nine-stranded β-sheet (β1–β9) of PmC11 consists of six parallel and three anti-parallel β-strands with 4↑3↓2↑1↑5↑6↑7↓8↓9↑ topology (Fig. 1A) and the overall structure includes 14 α-helices with six (α1–α2 and α4–α7) closely surrounding the β-sheet in an approximately parallel orientation. RESULTS
211 216 α1–α2 structure_element The central nine-stranded β-sheet (β1–β9) of PmC11 consists of six parallel and three anti-parallel β-strands with 4↑3↓2↑1↑5↑6↑7↓8↓9↑ topology (Fig. 1A) and the overall structure includes 14 α-helices with six (α1–α2 and α4–α7) closely surrounding the β-sheet in an approximately parallel orientation. RESULTS
221 226 α4–α7 structure_element The central nine-stranded β-sheet (β1–β9) of PmC11 consists of six parallel and three anti-parallel β-strands with 4↑3↓2↑1↑5↑6↑7↓8↓9↑ topology (Fig. 1A) and the overall structure includes 14 α-helices with six (α1–α2 and α4–α7) closely surrounding the β-sheet in an approximately parallel orientation. RESULTS
252 259 β-sheet structure_element The central nine-stranded β-sheet (β1–β9) of PmC11 consists of six parallel and three anti-parallel β-strands with 4↑3↓2↑1↑5↑6↑7↓8↓9↑ topology (Fig. 1A) and the overall structure includes 14 α-helices with six (α1–α2 and α4–α7) closely surrounding the β-sheet in an approximately parallel orientation. RESULTS
0 7 Helices structure_element Helices α1, α7, and α6 are located on one side of the β-sheet with α2, α4, and α5 on the opposite side (Fig. 1A). RESULTS
8 10 α1 structure_element Helices α1, α7, and α6 are located on one side of the β-sheet with α2, α4, and α5 on the opposite side (Fig. 1A). RESULTS
12 14 α7 structure_element Helices α1, α7, and α6 are located on one side of the β-sheet with α2, α4, and α5 on the opposite side (Fig. 1A). RESULTS
20 22 α6 structure_element Helices α1, α7, and α6 are located on one side of the β-sheet with α2, α4, and α5 on the opposite side (Fig. 1A). RESULTS
54 61 β-sheet structure_element Helices α1, α7, and α6 are located on one side of the β-sheet with α2, α4, and α5 on the opposite side (Fig. 1A). RESULTS
67 69 α2 structure_element Helices α1, α7, and α6 are located on one side of the β-sheet with α2, α4, and α5 on the opposite side (Fig. 1A). RESULTS
71 73 α4 structure_element Helices α1, α7, and α6 are located on one side of the β-sheet with α2, α4, and α5 on the opposite side (Fig. 1A). RESULTS
79 81 α5 structure_element Helices α1, α7, and α6 are located on one side of the β-sheet with α2, α4, and α5 on the opposite side (Fig. 1A). RESULTS
0 5 Helix structure_element Helix α3 sits at the end of the loop following β5 (L5), just preceding the Lys147 cleavage site, with both L5 and α3 pointing away from the central β-sheet and toward the CTD, which starts with α8. RESULTS
6 8 α3 structure_element Helix α3 sits at the end of the loop following β5 (L5), just preceding the Lys147 cleavage site, with both L5 and α3 pointing away from the central β-sheet and toward the CTD, which starts with α8. RESULTS
32 36 loop structure_element Helix α3 sits at the end of the loop following β5 (L5), just preceding the Lys147 cleavage site, with both L5 and α3 pointing away from the central β-sheet and toward the CTD, which starts with α8. RESULTS
47 49 β5 structure_element Helix α3 sits at the end of the loop following β5 (L5), just preceding the Lys147 cleavage site, with both L5 and α3 pointing away from the central β-sheet and toward the CTD, which starts with α8. RESULTS
51 53 L5 structure_element Helix α3 sits at the end of the loop following β5 (L5), just preceding the Lys147 cleavage site, with both L5 and α3 pointing away from the central β-sheet and toward the CTD, which starts with α8. RESULTS
75 81 Lys147 residue_name_number Helix α3 sits at the end of the loop following β5 (L5), just preceding the Lys147 cleavage site, with both L5 and α3 pointing away from the central β-sheet and toward the CTD, which starts with α8. RESULTS
82 95 cleavage site site Helix α3 sits at the end of the loop following β5 (L5), just preceding the Lys147 cleavage site, with both L5 and α3 pointing away from the central β-sheet and toward the CTD, which starts with α8. RESULTS
107 109 L5 structure_element Helix α3 sits at the end of the loop following β5 (L5), just preceding the Lys147 cleavage site, with both L5 and α3 pointing away from the central β-sheet and toward the CTD, which starts with α8. RESULTS
114 116 α3 structure_element Helix α3 sits at the end of the loop following β5 (L5), just preceding the Lys147 cleavage site, with both L5 and α3 pointing away from the central β-sheet and toward the CTD, which starts with α8. RESULTS
148 155 β-sheet structure_element Helix α3 sits at the end of the loop following β5 (L5), just preceding the Lys147 cleavage site, with both L5 and α3 pointing away from the central β-sheet and toward the CTD, which starts with α8. RESULTS
171 174 CTD structure_element Helix α3 sits at the end of the loop following β5 (L5), just preceding the Lys147 cleavage site, with both L5 and α3 pointing away from the central β-sheet and toward the CTD, which starts with α8. RESULTS
194 196 α8 structure_element Helix α3 sits at the end of the loop following β5 (L5), just preceding the Lys147 cleavage site, with both L5 and α3 pointing away from the central β-sheet and toward the CTD, which starts with α8. RESULTS
4 13 structure evidence The structure also includes two short β-hairpins (βA–βB and βD–βE) and a small β-sheet (βC–βF), which is formed from two distinct regions of the sequence (βC precedes α11, α12 and β9, whereas βF follows the βD-βE hairpin) in the middle of the CTD (Fig. 1B). RESULTS
38 48 β-hairpins structure_element The structure also includes two short β-hairpins (βA–βB and βD–βE) and a small β-sheet (βC–βF), which is formed from two distinct regions of the sequence (βC precedes α11, α12 and β9, whereas βF follows the βD-βE hairpin) in the middle of the CTD (Fig. 1B). RESULTS
50 55 βA–βB structure_element The structure also includes two short β-hairpins (βA–βB and βD–βE) and a small β-sheet (βC–βF), which is formed from two distinct regions of the sequence (βC precedes α11, α12 and β9, whereas βF follows the βD-βE hairpin) in the middle of the CTD (Fig. 1B). RESULTS
60 65 βD–βE structure_element The structure also includes two short β-hairpins (βA–βB and βD–βE) and a small β-sheet (βC–βF), which is formed from two distinct regions of the sequence (βC precedes α11, α12 and β9, whereas βF follows the βD-βE hairpin) in the middle of the CTD (Fig. 1B). RESULTS
73 86 small β-sheet structure_element The structure also includes two short β-hairpins (βA–βB and βD–βE) and a small β-sheet (βC–βF), which is formed from two distinct regions of the sequence (βC precedes α11, α12 and β9, whereas βF follows the βD-βE hairpin) in the middle of the CTD (Fig. 1B). RESULTS
88 93 βC–βF structure_element The structure also includes two short β-hairpins (βA–βB and βD–βE) and a small β-sheet (βC–βF), which is formed from two distinct regions of the sequence (βC precedes α11, α12 and β9, whereas βF follows the βD-βE hairpin) in the middle of the CTD (Fig. 1B). RESULTS
155 157 βC structure_element The structure also includes two short β-hairpins (βA–βB and βD–βE) and a small β-sheet (βC–βF), which is formed from two distinct regions of the sequence (βC precedes α11, α12 and β9, whereas βF follows the βD-βE hairpin) in the middle of the CTD (Fig. 1B). RESULTS
167 170 α11 structure_element The structure also includes two short β-hairpins (βA–βB and βD–βE) and a small β-sheet (βC–βF), which is formed from two distinct regions of the sequence (βC precedes α11, α12 and β9, whereas βF follows the βD-βE hairpin) in the middle of the CTD (Fig. 1B). RESULTS
172 175 α12 structure_element The structure also includes two short β-hairpins (βA–βB and βD–βE) and a small β-sheet (βC–βF), which is formed from two distinct regions of the sequence (βC precedes α11, α12 and β9, whereas βF follows the βD-βE hairpin) in the middle of the CTD (Fig. 1B). RESULTS
180 182 β9 structure_element The structure also includes two short β-hairpins (βA–βB and βD–βE) and a small β-sheet (βC–βF), which is formed from two distinct regions of the sequence (βC precedes α11, α12 and β9, whereas βF follows the βD-βE hairpin) in the middle of the CTD (Fig. 1B). RESULTS
192 194 βF structure_element The structure also includes two short β-hairpins (βA–βB and βD–βE) and a small β-sheet (βC–βF), which is formed from two distinct regions of the sequence (βC precedes α11, α12 and β9, whereas βF follows the βD-βE hairpin) in the middle of the CTD (Fig. 1B). RESULTS
207 212 βD-βE structure_element The structure also includes two short β-hairpins (βA–βB and βD–βE) and a small β-sheet (βC–βF), which is formed from two distinct regions of the sequence (βC precedes α11, α12 and β9, whereas βF follows the βD-βE hairpin) in the middle of the CTD (Fig. 1B). RESULTS
213 220 hairpin structure_element The structure also includes two short β-hairpins (βA–βB and βD–βE) and a small β-sheet (βC–βF), which is formed from two distinct regions of the sequence (βC precedes α11, α12 and β9, whereas βF follows the βD-βE hairpin) in the middle of the CTD (Fig. 1B). RESULTS
243 246 CTD structure_element The structure also includes two short β-hairpins (βA–βB and βD–βE) and a small β-sheet (βC–βF), which is formed from two distinct regions of the sequence (βC precedes α11, α12 and β9, whereas βF follows the βD-βE hairpin) in the middle of the CTD (Fig. 1B). RESULTS
0 17 Crystal structure evidence Crystal structure of a C11 peptidase from P. merdae. FIG
23 36 C11 peptidase protein_type Crystal structure of a C11 peptidase from P. merdae. FIG
42 51 P. merdae species Crystal structure of a C11 peptidase from P. merdae. FIG
4 30 primary sequence alignment experimental_method A, primary sequence alignment of PmC11 (Uniprot ID A7A9N3) and clostripain (Uniprot ID P09870) from C. histolyticum with identical residues highlighted in gray shading. FIG
34 39 PmC11 protein A, primary sequence alignment of PmC11 (Uniprot ID A7A9N3) and clostripain (Uniprot ID P09870) from C. histolyticum with identical residues highlighted in gray shading. FIG
64 75 clostripain protein A, primary sequence alignment of PmC11 (Uniprot ID A7A9N3) and clostripain (Uniprot ID P09870) from C. histolyticum with identical residues highlighted in gray shading. FIG
101 116 C. histolyticum species A, primary sequence alignment of PmC11 (Uniprot ID A7A9N3) and clostripain (Uniprot ID P09870) from C. histolyticum with identical residues highlighted in gray shading. FIG
27 32 PmC11 protein The secondary structure of PmC11 from the crystal structure is mapped onto its sequence with the position of the PmC11 catalytic dyad, autocatalytic cleavage site (Lys147), and S1 binding pocket Asp (Asp177) highlighted by a red star, a red downturned triangle, and a red upturned triangle, respectively. FIG
42 59 crystal structure evidence The secondary structure of PmC11 from the crystal structure is mapped onto its sequence with the position of the PmC11 catalytic dyad, autocatalytic cleavage site (Lys147), and S1 binding pocket Asp (Asp177) highlighted by a red star, a red downturned triangle, and a red upturned triangle, respectively. FIG
113 118 PmC11 protein The secondary structure of PmC11 from the crystal structure is mapped onto its sequence with the position of the PmC11 catalytic dyad, autocatalytic cleavage site (Lys147), and S1 binding pocket Asp (Asp177) highlighted by a red star, a red downturned triangle, and a red upturned triangle, respectively. FIG
119 133 catalytic dyad site The secondary structure of PmC11 from the crystal structure is mapped onto its sequence with the position of the PmC11 catalytic dyad, autocatalytic cleavage site (Lys147), and S1 binding pocket Asp (Asp177) highlighted by a red star, a red downturned triangle, and a red upturned triangle, respectively. FIG
135 162 autocatalytic cleavage site site The secondary structure of PmC11 from the crystal structure is mapped onto its sequence with the position of the PmC11 catalytic dyad, autocatalytic cleavage site (Lys147), and S1 binding pocket Asp (Asp177) highlighted by a red star, a red downturned triangle, and a red upturned triangle, respectively. FIG
164 170 Lys147 residue_name_number The secondary structure of PmC11 from the crystal structure is mapped onto its sequence with the position of the PmC11 catalytic dyad, autocatalytic cleavage site (Lys147), and S1 binding pocket Asp (Asp177) highlighted by a red star, a red downturned triangle, and a red upturned triangle, respectively. FIG
177 194 S1 binding pocket site The secondary structure of PmC11 from the crystal structure is mapped onto its sequence with the position of the PmC11 catalytic dyad, autocatalytic cleavage site (Lys147), and S1 binding pocket Asp (Asp177) highlighted by a red star, a red downturned triangle, and a red upturned triangle, respectively. FIG
195 198 Asp residue_name The secondary structure of PmC11 from the crystal structure is mapped onto its sequence with the position of the PmC11 catalytic dyad, autocatalytic cleavage site (Lys147), and S1 binding pocket Asp (Asp177) highlighted by a red star, a red downturned triangle, and a red upturned triangle, respectively. FIG
200 206 Asp177 residue_name_number The secondary structure of PmC11 from the crystal structure is mapped onto its sequence with the position of the PmC11 catalytic dyad, autocatalytic cleavage site (Lys147), and S1 binding pocket Asp (Asp177) highlighted by a red star, a red downturned triangle, and a red upturned triangle, respectively. FIG
11 16 loops structure_element Connecting loops are colored gray, the main β-sheet is in orange, with other strands in olive, α-helices are in blue, and the nonapeptide linker of clostripain that is excised upon autocleavage is underlined in red. FIG
44 51 β-sheet structure_element Connecting loops are colored gray, the main β-sheet is in orange, with other strands in olive, α-helices are in blue, and the nonapeptide linker of clostripain that is excised upon autocleavage is underlined in red. FIG
95 104 α-helices structure_element Connecting loops are colored gray, the main β-sheet is in orange, with other strands in olive, α-helices are in blue, and the nonapeptide linker of clostripain that is excised upon autocleavage is underlined in red. FIG
126 144 nonapeptide linker structure_element Connecting loops are colored gray, the main β-sheet is in orange, with other strands in olive, α-helices are in blue, and the nonapeptide linker of clostripain that is excised upon autocleavage is underlined in red. FIG
148 159 clostripain protein Connecting loops are colored gray, the main β-sheet is in orange, with other strands in olive, α-helices are in blue, and the nonapeptide linker of clostripain that is excised upon autocleavage is underlined in red. FIG
181 193 autocleavage ptm Connecting loops are colored gray, the main β-sheet is in orange, with other strands in olive, α-helices are in blue, and the nonapeptide linker of clostripain that is excised upon autocleavage is underlined in red. FIG
21 35 catalytic site site Sequences around the catalytic site of clostripain and PmC11 align well. FIG
39 50 clostripain protein Sequences around the catalytic site of clostripain and PmC11 align well. FIG
55 60 PmC11 protein Sequences around the catalytic site of clostripain and PmC11 align well. FIG
23 28 PmC11 protein B, topology diagram of PmC11 colored as in A except that additional (non-core) β-strands are in yellow. FIG
79 88 β-strands structure_element B, topology diagram of PmC11 colored as in A except that additional (non-core) β-strands are in yellow. FIG
44 51 β-sheet structure_element Helices found on either side of the central β-sheet are shown above and below the sheet, respectively. FIG
82 87 sheet structure_element Helices found on either side of the central β-sheet are shown above and below the sheet, respectively. FIG
20 34 catalytic dyad site The position of the catalytic dyad (H, C) and the processing site (Lys147) are highlighted. FIG
36 37 H residue_name The position of the catalytic dyad (H, C) and the processing site (Lys147) are highlighted. FIG
39 40 C residue_name The position of the catalytic dyad (H, C) and the processing site (Lys147) are highlighted. FIG
50 65 processing site site The position of the catalytic dyad (H, C) and the processing site (Lys147) are highlighted. FIG
67 73 Lys147 residue_name_number The position of the catalytic dyad (H, C) and the processing site (Lys147) are highlighted. FIG
19 28 β-strands structure_element Helices (1–14) and β-strands (1–9 and A-F) are numbered from the N terminus. FIG
4 21 core caspase-fold structure_element The core caspase-fold is highlighted in a box. FIG
25 30 PmC11 protein C, tertiary structure of PmC11. FIG
33 38 PmC11 protein The N and C termini (N and C) of PmC11 along with the central β-sheet (1–9), helix α5, and helices α8, α11, and α13 from the C-terminal domain, are all labeled. FIG
62 69 β-sheet structure_element The N and C termini (N and C) of PmC11 along with the central β-sheet (1–9), helix α5, and helices α8, α11, and α13 from the C-terminal domain, are all labeled. FIG
77 82 helix structure_element The N and C termini (N and C) of PmC11 along with the central β-sheet (1–9), helix α5, and helices α8, α11, and α13 from the C-terminal domain, are all labeled. FIG
83 85 α5 structure_element The N and C termini (N and C) of PmC11 along with the central β-sheet (1–9), helix α5, and helices α8, α11, and α13 from the C-terminal domain, are all labeled. FIG
91 98 helices structure_element The N and C termini (N and C) of PmC11 along with the central β-sheet (1–9), helix α5, and helices α8, α11, and α13 from the C-terminal domain, are all labeled. FIG
99 101 α8 structure_element The N and C termini (N and C) of PmC11 along with the central β-sheet (1–9), helix α5, and helices α8, α11, and α13 from the C-terminal domain, are all labeled. FIG
103 106 α11 structure_element The N and C termini (N and C) of PmC11 along with the central β-sheet (1–9), helix α5, and helices α8, α11, and α13 from the C-terminal domain, are all labeled. FIG
112 115 α13 structure_element The N and C termini (N and C) of PmC11 along with the central β-sheet (1–9), helix α5, and helices α8, α11, and α13 from the C-terminal domain, are all labeled. FIG
125 142 C-terminal domain structure_element The N and C termini (N and C) of PmC11 along with the central β-sheet (1–9), helix α5, and helices α8, α11, and α13 from the C-terminal domain, are all labeled. FIG
33 40 β-sheet structure_element Loops are colored gray, the main β-sheet is in orange, with other β-strands in yellow, and α-helices are in blue. FIG
66 75 β-strands structure_element Loops are colored gray, the main β-sheet is in orange, with other β-strands in yellow, and α-helices are in blue. FIG
91 100 α-helices structure_element Loops are colored gray, the main β-sheet is in orange, with other β-strands in yellow, and α-helices are in blue. FIG
4 7 CTD structure_element The CTD of PmC11 is composed of a tight helical bundle formed from helices α8–α14 and includes strands βC and βF, and β-hairpin βD–βE. The CTD sits entirely on one side of the enzyme interacting only with α3, α5, β9, and the loops surrounding β8. RESULTS
11 16 PmC11 protein The CTD of PmC11 is composed of a tight helical bundle formed from helices α8–α14 and includes strands βC and βF, and β-hairpin βD–βE. The CTD sits entirely on one side of the enzyme interacting only with α3, α5, β9, and the loops surrounding β8. RESULTS
34 54 tight helical bundle structure_element The CTD of PmC11 is composed of a tight helical bundle formed from helices α8–α14 and includes strands βC and βF, and β-hairpin βD–βE. The CTD sits entirely on one side of the enzyme interacting only with α3, α5, β9, and the loops surrounding β8. RESULTS
67 74 helices structure_element The CTD of PmC11 is composed of a tight helical bundle formed from helices α8–α14 and includes strands βC and βF, and β-hairpin βD–βE. The CTD sits entirely on one side of the enzyme interacting only with α3, α5, β9, and the loops surrounding β8. RESULTS
75 81 α8–α14 structure_element The CTD of PmC11 is composed of a tight helical bundle formed from helices α8–α14 and includes strands βC and βF, and β-hairpin βD–βE. The CTD sits entirely on one side of the enzyme interacting only with α3, α5, β9, and the loops surrounding β8. RESULTS
95 102 strands structure_element The CTD of PmC11 is composed of a tight helical bundle formed from helices α8–α14 and includes strands βC and βF, and β-hairpin βD–βE. The CTD sits entirely on one side of the enzyme interacting only with α3, α5, β9, and the loops surrounding β8. RESULTS
103 105 βC structure_element The CTD of PmC11 is composed of a tight helical bundle formed from helices α8–α14 and includes strands βC and βF, and β-hairpin βD–βE. The CTD sits entirely on one side of the enzyme interacting only with α3, α5, β9, and the loops surrounding β8. RESULTS
110 112 βF structure_element The CTD of PmC11 is composed of a tight helical bundle formed from helices α8–α14 and includes strands βC and βF, and β-hairpin βD–βE. The CTD sits entirely on one side of the enzyme interacting only with α3, α5, β9, and the loops surrounding β8. RESULTS
118 127 β-hairpin structure_element The CTD of PmC11 is composed of a tight helical bundle formed from helices α8–α14 and includes strands βC and βF, and β-hairpin βD–βE. The CTD sits entirely on one side of the enzyme interacting only with α3, α5, β9, and the loops surrounding β8. RESULTS
128 133 βD–βE structure_element The CTD of PmC11 is composed of a tight helical bundle formed from helices α8–α14 and includes strands βC and βF, and β-hairpin βD–βE. The CTD sits entirely on one side of the enzyme interacting only with α3, α5, β9, and the loops surrounding β8. RESULTS
139 142 CTD structure_element The CTD of PmC11 is composed of a tight helical bundle formed from helices α8–α14 and includes strands βC and βF, and β-hairpin βD–βE. The CTD sits entirely on one side of the enzyme interacting only with α3, α5, β9, and the loops surrounding β8. RESULTS
205 207 α3 structure_element The CTD of PmC11 is composed of a tight helical bundle formed from helices α8–α14 and includes strands βC and βF, and β-hairpin βD–βE. The CTD sits entirely on one side of the enzyme interacting only with α3, α5, β9, and the loops surrounding β8. RESULTS
209 211 α5 structure_element The CTD of PmC11 is composed of a tight helical bundle formed from helices α8–α14 and includes strands βC and βF, and β-hairpin βD–βE. The CTD sits entirely on one side of the enzyme interacting only with α3, α5, β9, and the loops surrounding β8. RESULTS
213 215 β9 structure_element The CTD of PmC11 is composed of a tight helical bundle formed from helices α8–α14 and includes strands βC and βF, and β-hairpin βD–βE. The CTD sits entirely on one side of the enzyme interacting only with α3, α5, β9, and the loops surrounding β8. RESULTS
225 230 loops structure_element The CTD of PmC11 is composed of a tight helical bundle formed from helices α8–α14 and includes strands βC and βF, and β-hairpin βD–βE. The CTD sits entirely on one side of the enzyme interacting only with α3, α5, β9, and the loops surrounding β8. RESULTS
243 245 β8 structure_element The CTD of PmC11 is composed of a tight helical bundle formed from helices α8–α14 and includes strands βC and βF, and β-hairpin βD–βE. The CTD sits entirely on one side of the enzyme interacting only with α3, α5, β9, and the loops surrounding β8. RESULTS
49 51 α5 structure_element Of the interacting secondary structure elements, α5 is perhaps the most interesting. RESULTS
0 10 This helix structure_element This helix makes a total of eight hydrogen bonds with the CTD, including one salt bridge (Arg191-Asp255) and is surrounded by the CTD on one side and the main core of the enzyme on the other, acting like a linchpin holding both components together (Fig. 1C). RESULTS
58 61 CTD structure_element This helix makes a total of eight hydrogen bonds with the CTD, including one salt bridge (Arg191-Asp255) and is surrounded by the CTD on one side and the main core of the enzyme on the other, acting like a linchpin holding both components together (Fig. 1C). RESULTS
90 96 Arg191 residue_name_number This helix makes a total of eight hydrogen bonds with the CTD, including one salt bridge (Arg191-Asp255) and is surrounded by the CTD on one side and the main core of the enzyme on the other, acting like a linchpin holding both components together (Fig. 1C). RESULTS
97 103 Asp255 residue_name_number This helix makes a total of eight hydrogen bonds with the CTD, including one salt bridge (Arg191-Asp255) and is surrounded by the CTD on one side and the main core of the enzyme on the other, acting like a linchpin holding both components together (Fig. 1C). RESULTS
130 133 CTD structure_element This helix makes a total of eight hydrogen bonds with the CTD, including one salt bridge (Arg191-Asp255) and is surrounded by the CTD on one side and the main core of the enzyme on the other, acting like a linchpin holding both components together (Fig. 1C). RESULTS
154 163 main core structure_element This helix makes a total of eight hydrogen bonds with the CTD, including one salt bridge (Arg191-Asp255) and is surrounded by the CTD on one side and the main core of the enzyme on the other, acting like a linchpin holding both components together (Fig. 1C). RESULTS
0 5 PmC11 protein PmC11 is, as expected, most structurally similar to other members of clan CD with the top hits in a search of known structures being caspase-7, gingipain-K, and legumain (PBD codes 4hq0, 4tkx, and 4aw9, respectively) (Table 2). RESULTS
69 76 clan CD protein_type PmC11 is, as expected, most structurally similar to other members of clan CD with the top hits in a search of known structures being caspase-7, gingipain-K, and legumain (PBD codes 4hq0, 4tkx, and 4aw9, respectively) (Table 2). RESULTS
116 126 structures evidence PmC11 is, as expected, most structurally similar to other members of clan CD with the top hits in a search of known structures being caspase-7, gingipain-K, and legumain (PBD codes 4hq0, 4tkx, and 4aw9, respectively) (Table 2). RESULTS
133 142 caspase-7 protein PmC11 is, as expected, most structurally similar to other members of clan CD with the top hits in a search of known structures being caspase-7, gingipain-K, and legumain (PBD codes 4hq0, 4tkx, and 4aw9, respectively) (Table 2). RESULTS
144 155 gingipain-K protein PmC11 is, as expected, most structurally similar to other members of clan CD with the top hits in a search of known structures being caspase-7, gingipain-K, and legumain (PBD codes 4hq0, 4tkx, and 4aw9, respectively) (Table 2). RESULTS
161 169 legumain protein PmC11 is, as expected, most structurally similar to other members of clan CD with the top hits in a search of known structures being caspase-7, gingipain-K, and legumain (PBD codes 4hq0, 4tkx, and 4aw9, respectively) (Table 2). RESULTS
4 21 C-terminal domain structure_element The C-terminal domain is unique to PmC11 within clan CD and structure comparisons for this domain alone does not produce any hits in the PDB (DaliLite, PDBeFold), suggesting a completely novel fold. RESULTS
35 40 PmC11 protein The C-terminal domain is unique to PmC11 within clan CD and structure comparisons for this domain alone does not produce any hits in the PDB (DaliLite, PDBeFold), suggesting a completely novel fold. RESULTS
48 55 clan CD protein_type The C-terminal domain is unique to PmC11 within clan CD and structure comparisons for this domain alone does not produce any hits in the PDB (DaliLite, PDBeFold), suggesting a completely novel fold. RESULTS
60 81 structure comparisons experimental_method The C-terminal domain is unique to PmC11 within clan CD and structure comparisons for this domain alone does not produce any hits in the PDB (DaliLite, PDBeFold), suggesting a completely novel fold. RESULTS
86 103 this domain alone structure_element The C-terminal domain is unique to PmC11 within clan CD and structure comparisons for this domain alone does not produce any hits in the PDB (DaliLite, PDBeFold), suggesting a completely novel fold. RESULTS
142 150 DaliLite experimental_method The C-terminal domain is unique to PmC11 within clan CD and structure comparisons for this domain alone does not produce any hits in the PDB (DaliLite, PDBeFold), suggesting a completely novel fold. RESULTS
152 160 PDBeFold experimental_method The C-terminal domain is unique to PmC11 within clan CD and structure comparisons for this domain alone does not produce any hits in the PDB (DaliLite, PDBeFold), suggesting a completely novel fold. RESULTS
59 66 clan CD protein_type As the archetypal and arguably most well studied member of clan CD, the caspases were used as the basis to investigate the structure/function relationships in PmC11, with caspase-7 as the representative member. RESULTS
72 80 caspases protein_type As the archetypal and arguably most well studied member of clan CD, the caspases were used as the basis to investigate the structure/function relationships in PmC11, with caspase-7 as the representative member. RESULTS
159 164 PmC11 protein As the archetypal and arguably most well studied member of clan CD, the caspases were used as the basis to investigate the structure/function relationships in PmC11, with caspase-7 as the representative member. RESULTS
171 180 caspase-7 protein As the archetypal and arguably most well studied member of clan CD, the caspases were used as the basis to investigate the structure/function relationships in PmC11, with caspase-7 as the representative member. RESULTS
19 28 β-strands structure_element Six of the central β-strands in PmC11 (β1–β2 and β5–β8) share the same topology as the six-stranded β-sheet found in caspases, with strands β3, β4, and β9 located on the outside of this core structure (Fig. 1B, box). RESULTS
32 37 PmC11 protein Six of the central β-strands in PmC11 (β1–β2 and β5–β8) share the same topology as the six-stranded β-sheet found in caspases, with strands β3, β4, and β9 located on the outside of this core structure (Fig. 1B, box). RESULTS
39 44 β1–β2 structure_element Six of the central β-strands in PmC11 (β1–β2 and β5–β8) share the same topology as the six-stranded β-sheet found in caspases, with strands β3, β4, and β9 located on the outside of this core structure (Fig. 1B, box). RESULTS
49 54 β5–β8 structure_element Six of the central β-strands in PmC11 (β1–β2 and β5–β8) share the same topology as the six-stranded β-sheet found in caspases, with strands β3, β4, and β9 located on the outside of this core structure (Fig. 1B, box). RESULTS
87 107 six-stranded β-sheet structure_element Six of the central β-strands in PmC11 (β1–β2 and β5–β8) share the same topology as the six-stranded β-sheet found in caspases, with strands β3, β4, and β9 located on the outside of this core structure (Fig. 1B, box). RESULTS
117 125 caspases protein_type Six of the central β-strands in PmC11 (β1–β2 and β5–β8) share the same topology as the six-stranded β-sheet found in caspases, with strands β3, β4, and β9 located on the outside of this core structure (Fig. 1B, box). RESULTS
132 139 strands structure_element Six of the central β-strands in PmC11 (β1–β2 and β5–β8) share the same topology as the six-stranded β-sheet found in caspases, with strands β3, β4, and β9 located on the outside of this core structure (Fig. 1B, box). RESULTS
140 142 β3 structure_element Six of the central β-strands in PmC11 (β1–β2 and β5–β8) share the same topology as the six-stranded β-sheet found in caspases, with strands β3, β4, and β9 located on the outside of this core structure (Fig. 1B, box). RESULTS
144 146 β4 structure_element Six of the central β-strands in PmC11 (β1–β2 and β5–β8) share the same topology as the six-stranded β-sheet found in caspases, with strands β3, β4, and β9 located on the outside of this core structure (Fig. 1B, box). RESULTS
152 154 β9 structure_element Six of the central β-strands in PmC11 (β1–β2 and β5–β8) share the same topology as the six-stranded β-sheet found in caspases, with strands β3, β4, and β9 located on the outside of this core structure (Fig. 1B, box). RESULTS
186 200 core structure structure_element Six of the central β-strands in PmC11 (β1–β2 and β5–β8) share the same topology as the six-stranded β-sheet found in caspases, with strands β3, β4, and β9 located on the outside of this core structure (Fig. 1B, box). RESULTS
0 6 His133 residue_name_number His133 and Cys179 were found at locations structurally homologous to the caspase catalytic dyad, and other clan CD structures, at the C termini of strands β5 and β6, respectively (Figs. 1, A and B, and 2A). RESULTS
11 17 Cys179 residue_name_number His133 and Cys179 were found at locations structurally homologous to the caspase catalytic dyad, and other clan CD structures, at the C termini of strands β5 and β6, respectively (Figs. 1, A and B, and 2A). RESULTS
73 80 caspase protein_type His133 and Cys179 were found at locations structurally homologous to the caspase catalytic dyad, and other clan CD structures, at the C termini of strands β5 and β6, respectively (Figs. 1, A and B, and 2A). RESULTS
81 95 catalytic dyad site His133 and Cys179 were found at locations structurally homologous to the caspase catalytic dyad, and other clan CD structures, at the C termini of strands β5 and β6, respectively (Figs. 1, A and B, and 2A). RESULTS
107 114 clan CD protein_type His133 and Cys179 were found at locations structurally homologous to the caspase catalytic dyad, and other clan CD structures, at the C termini of strands β5 and β6, respectively (Figs. 1, A and B, and 2A). RESULTS
115 125 structures evidence His133 and Cys179 were found at locations structurally homologous to the caspase catalytic dyad, and other clan CD structures, at the C termini of strands β5 and β6, respectively (Figs. 1, A and B, and 2A). RESULTS
147 154 strands structure_element His133 and Cys179 were found at locations structurally homologous to the caspase catalytic dyad, and other clan CD structures, at the C termini of strands β5 and β6, respectively (Figs. 1, A and B, and 2A). RESULTS
155 157 β5 structure_element His133 and Cys179 were found at locations structurally homologous to the caspase catalytic dyad, and other clan CD structures, at the C termini of strands β5 and β6, respectively (Figs. 1, A and B, and 2A). RESULTS
162 164 β6 structure_element His133 and Cys179 were found at locations structurally homologous to the caspase catalytic dyad, and other clan CD structures, at the C termini of strands β5 and β6, respectively (Figs. 1, A and B, and 2A). RESULTS
2 29 multiple sequence alignment experimental_method A multiple sequence alignment of C11 proteins revealed that these residues are highly conserved (data not shown). RESULTS
33 36 C11 protein_type A multiple sequence alignment of C11 proteins revealed that these residues are highly conserved (data not shown). RESULTS
79 95 highly conserved protein_state A multiple sequence alignment of C11 proteins revealed that these residues are highly conserved (data not shown). RESULTS
11 33 PDBeFOLD superposition experimental_method Summary of PDBeFOLD superposition of structures found to be most similar to PmC11 in the PBD based on DaliLite TABLE
76 81 PmC11 protein Summary of PDBeFOLD superposition of structures found to be most similar to PmC11 in the PBD based on DaliLite TABLE
102 110 DaliLite experimental_method Summary of PDBeFOLD superposition of structures found to be most similar to PmC11 in the PBD based on DaliLite TABLE
0 43 Biochemical and structural characterization experimental_method Biochemical and structural characterization of PmC11. FIG
47 52 PmC11 protein Biochemical and structural characterization of PmC11. FIG
54 59 PmC11 protein A, ribbon representation of the overall structure of PmC11 illustrating the catalytic site, cleavage site displacement, and potential S1 binding site. FIG
77 91 catalytic site site A, ribbon representation of the overall structure of PmC11 illustrating the catalytic site, cleavage site displacement, and potential S1 binding site. FIG
135 150 S1 binding site site A, ribbon representation of the overall structure of PmC11 illustrating the catalytic site, cleavage site displacement, and potential S1 binding site. FIG
12 21 structure evidence The overall structure of PmC11 is shown in gray, looking down into the catalytic site with the catalytic dyad in red. FIG
25 30 PmC11 protein The overall structure of PmC11 is shown in gray, looking down into the catalytic site with the catalytic dyad in red. FIG
71 85 catalytic site site The overall structure of PmC11 is shown in gray, looking down into the catalytic site with the catalytic dyad in red. FIG
95 109 catalytic dyad site The overall structure of PmC11 is shown in gray, looking down into the catalytic site with the catalytic dyad in red. FIG
20 43 autolytic cleavage site site The two ends of the autolytic cleavage site (Lys147 and Ala148, green) are displaced by 19.5 Å (thin black line) from one another and residues in the potential substrate binding pocket are highlighted in blue. FIG
45 51 Lys147 residue_name_number The two ends of the autolytic cleavage site (Lys147 and Ala148, green) are displaced by 19.5 Å (thin black line) from one another and residues in the potential substrate binding pocket are highlighted in blue. FIG
45 51 Lys147 residue_name_number The two ends of the autolytic cleavage site (Lys147 and Ala148, green) are displaced by 19.5 Å (thin black line) from one another and residues in the potential substrate binding pocket are highlighted in blue. FIG
56 62 Ala148 residue_name_number The two ends of the autolytic cleavage site (Lys147 and Ala148, green) are displaced by 19.5 Å (thin black line) from one another and residues in the potential substrate binding pocket are highlighted in blue. FIG
160 184 substrate binding pocket site The two ends of the autolytic cleavage site (Lys147 and Ala148, green) are displaced by 19.5 Å (thin black line) from one another and residues in the potential substrate binding pocket are highlighted in blue. FIG
3 32 size exclusion chromatography experimental_method B, size exclusion chromatography of PmC11. FIG
36 41 PmC11 protein B, size exclusion chromatography of PmC11. FIG
20 27 monomer oligomeric_state PmC11 migrates as a monomer with a molecular mass around 41 kDa calculated from protein standards of known molecular weights. FIG
63 71 SDS-PAGE experimental_method Elution fractions across the major peak (1–6) were analyzed by SDS-PAGE on a 4–12% gel in MES buffer. FIG
7 13 active protein_state C, the active form of PmC11 and two mutants, PmC11C179A (C) and PmC11K147A (K), were examined by SDS-PAGE (lane 1) and Western blot analysis using an anti-His antibody (lane 2) show that PmC11 autoprocesses, whereas mutants, PmC11C179A and PmC11K147A, do not show autoprocessing in vitro. FIG
22 27 PmC11 protein C, the active form of PmC11 and two mutants, PmC11C179A (C) and PmC11K147A (K), were examined by SDS-PAGE (lane 1) and Western blot analysis using an anti-His antibody (lane 2) show that PmC11 autoprocesses, whereas mutants, PmC11C179A and PmC11K147A, do not show autoprocessing in vitro. FIG
45 55 PmC11C179A mutant C, the active form of PmC11 and two mutants, PmC11C179A (C) and PmC11K147A (K), were examined by SDS-PAGE (lane 1) and Western blot analysis using an anti-His antibody (lane 2) show that PmC11 autoprocesses, whereas mutants, PmC11C179A and PmC11K147A, do not show autoprocessing in vitro. FIG
64 74 PmC11K147A mutant C, the active form of PmC11 and two mutants, PmC11C179A (C) and PmC11K147A (K), were examined by SDS-PAGE (lane 1) and Western blot analysis using an anti-His antibody (lane 2) show that PmC11 autoprocesses, whereas mutants, PmC11C179A and PmC11K147A, do not show autoprocessing in vitro. FIG
97 105 SDS-PAGE experimental_method C, the active form of PmC11 and two mutants, PmC11C179A (C) and PmC11K147A (K), were examined by SDS-PAGE (lane 1) and Western blot analysis using an anti-His antibody (lane 2) show that PmC11 autoprocesses, whereas mutants, PmC11C179A and PmC11K147A, do not show autoprocessing in vitro. FIG
119 131 Western blot experimental_method C, the active form of PmC11 and two mutants, PmC11C179A (C) and PmC11K147A (K), were examined by SDS-PAGE (lane 1) and Western blot analysis using an anti-His antibody (lane 2) show that PmC11 autoprocesses, whereas mutants, PmC11C179A and PmC11K147A, do not show autoprocessing in vitro. FIG
187 192 PmC11 protein C, the active form of PmC11 and two mutants, PmC11C179A (C) and PmC11K147A (K), were examined by SDS-PAGE (lane 1) and Western blot analysis using an anti-His antibody (lane 2) show that PmC11 autoprocesses, whereas mutants, PmC11C179A and PmC11K147A, do not show autoprocessing in vitro. FIG
193 206 autoprocesses ptm C, the active form of PmC11 and two mutants, PmC11C179A (C) and PmC11K147A (K), were examined by SDS-PAGE (lane 1) and Western blot analysis using an anti-His antibody (lane 2) show that PmC11 autoprocesses, whereas mutants, PmC11C179A and PmC11K147A, do not show autoprocessing in vitro. FIG
225 235 PmC11C179A mutant C, the active form of PmC11 and two mutants, PmC11C179A (C) and PmC11K147A (K), were examined by SDS-PAGE (lane 1) and Western blot analysis using an anti-His antibody (lane 2) show that PmC11 autoprocesses, whereas mutants, PmC11C179A and PmC11K147A, do not show autoprocessing in vitro. FIG
240 250 PmC11K147A mutant C, the active form of PmC11 and two mutants, PmC11C179A (C) and PmC11K147A (K), were examined by SDS-PAGE (lane 1) and Western blot analysis using an anti-His antibody (lane 2) show that PmC11 autoprocesses, whereas mutants, PmC11C179A and PmC11K147A, do not show autoprocessing in vitro. FIG
264 278 autoprocessing ptm C, the active form of PmC11 and two mutants, PmC11C179A (C) and PmC11K147A (K), were examined by SDS-PAGE (lane 1) and Western blot analysis using an anti-His antibody (lane 2) show that PmC11 autoprocesses, whereas mutants, PmC11C179A and PmC11K147A, do not show autoprocessing in vitro. FIG
34 39 PmC11 protein D, cysteine peptidase activity of PmC11. FIG
7 11 Vmax evidence Km and Vmax of PmC11 and K147A mutant were determined by monitoring change in the fluorescence corresponding to AMC release from Bz-R-AMC. FIG
15 20 PmC11 protein Km and Vmax of PmC11 and K147A mutant were determined by monitoring change in the fluorescence corresponding to AMC release from Bz-R-AMC. FIG
25 30 K147A mutant Km and Vmax of PmC11 and K147A mutant were determined by monitoring change in the fluorescence corresponding to AMC release from Bz-R-AMC. FIG
129 137 Bz-R-AMC chemical Km and Vmax of PmC11 and K147A mutant were determined by monitoring change in the fluorescence corresponding to AMC release from Bz-R-AMC. FIG
3 28 intermolecular processing ptm E, intermolecular processing of PmC11C179A by PmC11. FIG
32 42 PmC11C179A mutant E, intermolecular processing of PmC11C179A by PmC11. FIG
46 51 PmC11 protein E, intermolecular processing of PmC11C179A by PmC11. FIG
89 94 PmC11 protein PmC11C179A (20 μg) was incubated overnight at 37 °C with increasing amounts of processed PmC11 and analyzed on a 10% SDS-PAGE gel. FIG
117 125 SDS-PAGE experimental_method PmC11C179A (20 μg) was incubated overnight at 37 °C with increasing amounts of processed PmC11 and analyzed on a 10% SDS-PAGE gel. FIG
9 19 PmC11C179A mutant Inactive PmC11C179A was not processed to a major extent by active PmC11 until around a ratio of 1:4 (5 μg of active PmC11). FIG
59 65 active protein_state Inactive PmC11C179A was not processed to a major extent by active PmC11 until around a ratio of 1:4 (5 μg of active PmC11). FIG
66 71 PmC11 protein Inactive PmC11C179A was not processed to a major extent by active PmC11 until around a ratio of 1:4 (5 μg of active PmC11). FIG
109 115 active protein_state Inactive PmC11C179A was not processed to a major extent by active PmC11 until around a ratio of 1:4 (5 μg of active PmC11). FIG
116 121 PmC11 protein Inactive PmC11C179A was not processed to a major extent by active PmC11 until around a ratio of 1:4 (5 μg of active PmC11). FIG
26 32 active protein_state A single lane of 20 μg of active PmC11 (labeled 20) is shown for comparison. FIG
33 38 PmC11 protein A single lane of 20 μg of active PmC11 (labeled 20) is shown for comparison. FIG
3 11 activity evidence F, activity of PmC11 against basic substrates. FIG
15 20 PmC11 protein F, activity of PmC11 against basic substrates. FIG
38 43 PmC11 protein G, electrostatic surface potential of PmC11 shown in a similar orientation, where blue and red denote positively and negatively charged surface potential, respectively, contoured at ±5 kT/e. FIG
20 34 catalytic dyad site The position of the catalytic dyad, one potential key substrate binding residue Asp177, and the ends of the cleavage site Lys147 and Ala148 are indicated. FIG
50 79 key substrate binding residue site The position of the catalytic dyad, one potential key substrate binding residue Asp177, and the ends of the cleavage site Lys147 and Ala148 are indicated. FIG
80 86 Asp177 residue_name_number The position of the catalytic dyad, one potential key substrate binding residue Asp177, and the ends of the cleavage site Lys147 and Ala148 are indicated. FIG
108 121 cleavage site site The position of the catalytic dyad, one potential key substrate binding residue Asp177, and the ends of the cleavage site Lys147 and Ala148 are indicated. FIG
122 128 Lys147 residue_name_number The position of the catalytic dyad, one potential key substrate binding residue Asp177, and the ends of the cleavage site Lys147 and Ala148 are indicated. FIG
133 139 Ala148 residue_name_number The position of the catalytic dyad, one potential key substrate binding residue Asp177, and the ends of the cleavage site Lys147 and Ala148 are indicated. FIG
12 21 α-helices structure_element Five of the α-helices surrounding the β-sheet of PmC11 (α1, α2, α4, α6, and α7) are found in similar positions to the five structurally conserved helices in caspases and other members of clan CD, apart from family C80. RESULTS
38 45 β-sheet structure_element Five of the α-helices surrounding the β-sheet of PmC11 (α1, α2, α4, α6, and α7) are found in similar positions to the five structurally conserved helices in caspases and other members of clan CD, apart from family C80. RESULTS
49 54 PmC11 protein Five of the α-helices surrounding the β-sheet of PmC11 (α1, α2, α4, α6, and α7) are found in similar positions to the five structurally conserved helices in caspases and other members of clan CD, apart from family C80. RESULTS
56 58 α1 structure_element Five of the α-helices surrounding the β-sheet of PmC11 (α1, α2, α4, α6, and α7) are found in similar positions to the five structurally conserved helices in caspases and other members of clan CD, apart from family C80. RESULTS
60 62 α2 structure_element Five of the α-helices surrounding the β-sheet of PmC11 (α1, α2, α4, α6, and α7) are found in similar positions to the five structurally conserved helices in caspases and other members of clan CD, apart from family C80. RESULTS
64 66 α4 structure_element Five of the α-helices surrounding the β-sheet of PmC11 (α1, α2, α4, α6, and α7) are found in similar positions to the five structurally conserved helices in caspases and other members of clan CD, apart from family C80. RESULTS
68 70 α6 structure_element Five of the α-helices surrounding the β-sheet of PmC11 (α1, α2, α4, α6, and α7) are found in similar positions to the five structurally conserved helices in caspases and other members of clan CD, apart from family C80. RESULTS
76 78 α7 structure_element Five of the α-helices surrounding the β-sheet of PmC11 (α1, α2, α4, α6, and α7) are found in similar positions to the five structurally conserved helices in caspases and other members of clan CD, apart from family C80. RESULTS
123 145 structurally conserved protein_state Five of the α-helices surrounding the β-sheet of PmC11 (α1, α2, α4, α6, and α7) are found in similar positions to the five structurally conserved helices in caspases and other members of clan CD, apart from family C80. RESULTS
146 153 helices structure_element Five of the α-helices surrounding the β-sheet of PmC11 (α1, α2, α4, α6, and α7) are found in similar positions to the five structurally conserved helices in caspases and other members of clan CD, apart from family C80. RESULTS
157 165 caspases protein_type Five of the α-helices surrounding the β-sheet of PmC11 (α1, α2, α4, α6, and α7) are found in similar positions to the five structurally conserved helices in caspases and other members of clan CD, apart from family C80. RESULTS
187 194 clan CD protein_type Five of the α-helices surrounding the β-sheet of PmC11 (α1, α2, α4, α6, and α7) are found in similar positions to the five structurally conserved helices in caspases and other members of clan CD, apart from family C80. RESULTS
214 217 C80 protein_type Five of the α-helices surrounding the β-sheet of PmC11 (α1, α2, α4, α6, and α7) are found in similar positions to the five structurally conserved helices in caspases and other members of clan CD, apart from family C80. RESULTS
20 36 extended β-sheet structure_element Other than its more extended β-sheet, PmC11 differs most significantly from other clan CD members at its C terminus, where the CTD contains a further seven α-helices and four β-strands after β8. RESULTS
38 43 PmC11 protein Other than its more extended β-sheet, PmC11 differs most significantly from other clan CD members at its C terminus, where the CTD contains a further seven α-helices and four β-strands after β8. RESULTS
82 89 clan CD protein_type Other than its more extended β-sheet, PmC11 differs most significantly from other clan CD members at its C terminus, where the CTD contains a further seven α-helices and four β-strands after β8. RESULTS
127 130 CTD structure_element Other than its more extended β-sheet, PmC11 differs most significantly from other clan CD members at its C terminus, where the CTD contains a further seven α-helices and four β-strands after β8. RESULTS
156 165 α-helices structure_element Other than its more extended β-sheet, PmC11 differs most significantly from other clan CD members at its C terminus, where the CTD contains a further seven α-helices and four β-strands after β8. RESULTS
175 184 β-strands structure_element Other than its more extended β-sheet, PmC11 differs most significantly from other clan CD members at its C terminus, where the CTD contains a further seven α-helices and four β-strands after β8. RESULTS
191 193 β8 structure_element Other than its more extended β-sheet, PmC11 differs most significantly from other clan CD members at its C terminus, where the CTD contains a further seven α-helices and four β-strands after β8. RESULTS
0 14 Autoprocessing ptm Autoprocessing of PmC11 RESULTS
18 23 PmC11 protein Autoprocessing of PmC11 RESULTS
0 12 Purification experimental_method Purification of recombinant PmC11 (molecular mass = 42.6 kDa) revealed partial processing into two cleavage products of 26.4 and 16.2 kDa, related to the observed cleavage at Lys147 in the crystal structure (Fig. 2A). RESULTS
28 33 PmC11 protein Purification of recombinant PmC11 (molecular mass = 42.6 kDa) revealed partial processing into two cleavage products of 26.4 and 16.2 kDa, related to the observed cleavage at Lys147 in the crystal structure (Fig. 2A). RESULTS
163 171 cleavage ptm Purification of recombinant PmC11 (molecular mass = 42.6 kDa) revealed partial processing into two cleavage products of 26.4 and 16.2 kDa, related to the observed cleavage at Lys147 in the crystal structure (Fig. 2A). RESULTS
175 181 Lys147 residue_name_number Purification of recombinant PmC11 (molecular mass = 42.6 kDa) revealed partial processing into two cleavage products of 26.4 and 16.2 kDa, related to the observed cleavage at Lys147 in the crystal structure (Fig. 2A). RESULTS
189 206 crystal structure evidence Purification of recombinant PmC11 (molecular mass = 42.6 kDa) revealed partial processing into two cleavage products of 26.4 and 16.2 kDa, related to the observed cleavage at Lys147 in the crystal structure (Fig. 2A). RESULTS
0 10 Incubation experimental_method Incubation of PmC11 at 37 °C for 16 h, resulted in a fully processed enzyme that remained as an intact monomer when applied to a size-exclusion column (Fig. 2B). RESULTS
14 19 PmC11 protein Incubation of PmC11 at 37 °C for 16 h, resulted in a fully processed enzyme that remained as an intact monomer when applied to a size-exclusion column (Fig. 2B). RESULTS
53 68 fully processed protein_state Incubation of PmC11 at 37 °C for 16 h, resulted in a fully processed enzyme that remained as an intact monomer when applied to a size-exclusion column (Fig. 2B). RESULTS
96 102 intact protein_state Incubation of PmC11 at 37 °C for 16 h, resulted in a fully processed enzyme that remained as an intact monomer when applied to a size-exclusion column (Fig. 2B). RESULTS
103 110 monomer oligomeric_state Incubation of PmC11 at 37 °C for 16 h, resulted in a fully processed enzyme that remained as an intact monomer when applied to a size-exclusion column (Fig. 2B). RESULTS
11 24 cleavage site site The single cleavage site of PmC11 at Lys147 is found immediately after α3, in loop L5 within the central β-sheet (Figs. 1, A and B, and 2A). RESULTS
28 33 PmC11 protein The single cleavage site of PmC11 at Lys147 is found immediately after α3, in loop L5 within the central β-sheet (Figs. 1, A and B, and 2A). RESULTS
37 43 Lys147 residue_name_number The single cleavage site of PmC11 at Lys147 is found immediately after α3, in loop L5 within the central β-sheet (Figs. 1, A and B, and 2A). RESULTS
71 73 α3 structure_element The single cleavage site of PmC11 at Lys147 is found immediately after α3, in loop L5 within the central β-sheet (Figs. 1, A and B, and 2A). RESULTS
78 82 loop structure_element The single cleavage site of PmC11 at Lys147 is found immediately after α3, in loop L5 within the central β-sheet (Figs. 1, A and B, and 2A). RESULTS
83 85 L5 structure_element The single cleavage site of PmC11 at Lys147 is found immediately after α3, in loop L5 within the central β-sheet (Figs. 1, A and B, and 2A). RESULTS
105 112 β-sheet structure_element The single cleavage site of PmC11 at Lys147 is found immediately after α3, in loop L5 within the central β-sheet (Figs. 1, A and B, and 2A). RESULTS
20 33 cleavage site site The two ends of the cleavage site are remarkably well ordered in the crystal structure and displaced from one another by 19.5 Å (Fig. 2A). RESULTS
69 86 crystal structure evidence The two ends of the cleavage site are remarkably well ordered in the crystal structure and displaced from one another by 19.5 Å (Fig. 2A). RESULTS
37 50 cleavage site site Moreover, the C-terminal side of the cleavage site resides near the catalytic dyad with Ala148 being 4.5 and 5.7 Å from His133 and Cys179, respectively. RESULTS
68 82 catalytic dyad site Moreover, the C-terminal side of the cleavage site resides near the catalytic dyad with Ala148 being 4.5 and 5.7 Å from His133 and Cys179, respectively. RESULTS
88 94 Ala148 residue_name_number Moreover, the C-terminal side of the cleavage site resides near the catalytic dyad with Ala148 being 4.5 and 5.7 Å from His133 and Cys179, respectively. RESULTS
120 126 His133 residue_name_number Moreover, the C-terminal side of the cleavage site resides near the catalytic dyad with Ala148 being 4.5 and 5.7 Å from His133 and Cys179, respectively. RESULTS
131 137 Cys179 residue_name_number Moreover, the C-terminal side of the cleavage site resides near the catalytic dyad with Ala148 being 4.5 and 5.7 Å from His133 and Cys179, respectively. RESULTS
43 48 helix structure_element Consequently, it appears feasible that the helix attached to Lys147 (α3) could be responsible for steric autoinhibition of PmC11 when Lys147 is covalently bonded to Ala148. RESULTS
61 67 Lys147 residue_name_number Consequently, it appears feasible that the helix attached to Lys147 (α3) could be responsible for steric autoinhibition of PmC11 when Lys147 is covalently bonded to Ala148. RESULTS
69 71 α3 structure_element Consequently, it appears feasible that the helix attached to Lys147 (α3) could be responsible for steric autoinhibition of PmC11 when Lys147 is covalently bonded to Ala148. RESULTS
123 128 PmC11 protein Consequently, it appears feasible that the helix attached to Lys147 (α3) could be responsible for steric autoinhibition of PmC11 when Lys147 is covalently bonded to Ala148. RESULTS
134 140 Lys147 residue_name_number Consequently, it appears feasible that the helix attached to Lys147 (α3) could be responsible for steric autoinhibition of PmC11 when Lys147 is covalently bonded to Ala148. RESULTS
165 171 Ala148 residue_name_number Consequently, it appears feasible that the helix attached to Lys147 (α3) could be responsible for steric autoinhibition of PmC11 when Lys147 is covalently bonded to Ala148. RESULTS
10 18 cleavage ptm Thus, the cleavage would be required for full activation of PmC11. RESULTS
41 56 full activation protein_state Thus, the cleavage would be required for full activation of PmC11. RESULTS
60 65 PmC11 protein Thus, the cleavage would be required for full activation of PmC11. RESULTS
78 88 PmC11C179A mutant To investigate this possibility, two mutant forms of the enzyme were created: PmC11C179A (a catalytically inactive mutant) and PmC11K147A (a cleavage-site mutant). RESULTS
92 121 catalytically inactive mutant protein_state To investigate this possibility, two mutant forms of the enzyme were created: PmC11C179A (a catalytically inactive mutant) and PmC11K147A (a cleavage-site mutant). RESULTS
127 137 PmC11K147A mutant To investigate this possibility, two mutant forms of the enzyme were created: PmC11C179A (a catalytically inactive mutant) and PmC11K147A (a cleavage-site mutant). RESULTS
141 161 cleavage-site mutant protein_state To investigate this possibility, two mutant forms of the enzyme were created: PmC11C179A (a catalytically inactive mutant) and PmC11K147A (a cleavage-site mutant). RESULTS
8 16 SDS-PAGE experimental_method Initial SDS-PAGE and Western blot analysis of both mutants revealed no discernible processing occurred as compared with active PmC11 (Fig. 2C). RESULTS
21 33 Western blot experimental_method Initial SDS-PAGE and Western blot analysis of both mutants revealed no discernible processing occurred as compared with active PmC11 (Fig. 2C). RESULTS
120 126 active protein_state Initial SDS-PAGE and Western blot analysis of both mutants revealed no discernible processing occurred as compared with active PmC11 (Fig. 2C). RESULTS
127 132 PmC11 protein Initial SDS-PAGE and Western blot analysis of both mutants revealed no discernible processing occurred as compared with active PmC11 (Fig. 2C). RESULTS
4 14 PmC11K147A mutant The PmC11K147A mutant enzyme had a markedly different reaction rate (Vmax) compared with WT, where the reaction velocity of PmC11 was 10 times greater than that of PmC11K147A (Fig. 2D). RESULTS
15 21 mutant protein_state The PmC11K147A mutant enzyme had a markedly different reaction rate (Vmax) compared with WT, where the reaction velocity of PmC11 was 10 times greater than that of PmC11K147A (Fig. 2D). RESULTS
54 67 reaction rate evidence The PmC11K147A mutant enzyme had a markedly different reaction rate (Vmax) compared with WT, where the reaction velocity of PmC11 was 10 times greater than that of PmC11K147A (Fig. 2D). RESULTS
69 73 Vmax evidence The PmC11K147A mutant enzyme had a markedly different reaction rate (Vmax) compared with WT, where the reaction velocity of PmC11 was 10 times greater than that of PmC11K147A (Fig. 2D). RESULTS
89 91 WT protein_state The PmC11K147A mutant enzyme had a markedly different reaction rate (Vmax) compared with WT, where the reaction velocity of PmC11 was 10 times greater than that of PmC11K147A (Fig. 2D). RESULTS
103 120 reaction velocity evidence The PmC11K147A mutant enzyme had a markedly different reaction rate (Vmax) compared with WT, where the reaction velocity of PmC11 was 10 times greater than that of PmC11K147A (Fig. 2D). RESULTS
124 129 PmC11 protein The PmC11K147A mutant enzyme had a markedly different reaction rate (Vmax) compared with WT, where the reaction velocity of PmC11 was 10 times greater than that of PmC11K147A (Fig. 2D). RESULTS
164 174 PmC11K147A mutant The PmC11K147A mutant enzyme had a markedly different reaction rate (Vmax) compared with WT, where the reaction velocity of PmC11 was 10 times greater than that of PmC11K147A (Fig. 2D). RESULTS
39 44 PmC11 protein Taken together, these data reveal that PmC11 requires processing at Lys147 for optimum activity. RESULTS
68 74 Lys147 residue_name_number Taken together, these data reveal that PmC11 requires processing at Lys147 for optimum activity. RESULTS
88 98 PmC11C179A mutant To investigate whether processing is a result of intra- or intermolecular cleavage, the PmC11C179A mutant was incubated with increasing concentrations of processed and activated PmC11. RESULTS
99 105 mutant protein_state To investigate whether processing is a result of intra- or intermolecular cleavage, the PmC11C179A mutant was incubated with increasing concentrations of processed and activated PmC11. RESULTS
110 150 incubated with increasing concentrations experimental_method To investigate whether processing is a result of intra- or intermolecular cleavage, the PmC11C179A mutant was incubated with increasing concentrations of processed and activated PmC11. RESULTS
154 163 processed protein_state To investigate whether processing is a result of intra- or intermolecular cleavage, the PmC11C179A mutant was incubated with increasing concentrations of processed and activated PmC11. RESULTS
168 177 activated protein_state To investigate whether processing is a result of intra- or intermolecular cleavage, the PmC11C179A mutant was incubated with increasing concentrations of processed and activated PmC11. RESULTS
178 183 PmC11 protein To investigate whether processing is a result of intra- or intermolecular cleavage, the PmC11C179A mutant was incubated with increasing concentrations of processed and activated PmC11. RESULTS
62 72 PmC11C179A mutant These studies revealed that there was no apparent cleavage of PmC11C179A by the active enzyme at low concentrations of PmC11 and that only limited cleavage was observed when the ratio of active enzyme (PmC11:PmC11C179A) was increased to ∼1:10 and 1:4, with complete cleavage observed at a ratio of 1:1 (Fig. 2E). RESULTS
80 86 active protein_state These studies revealed that there was no apparent cleavage of PmC11C179A by the active enzyme at low concentrations of PmC11 and that only limited cleavage was observed when the ratio of active enzyme (PmC11:PmC11C179A) was increased to ∼1:10 and 1:4, with complete cleavage observed at a ratio of 1:1 (Fig. 2E). RESULTS
94 115 at low concentrations experimental_method These studies revealed that there was no apparent cleavage of PmC11C179A by the active enzyme at low concentrations of PmC11 and that only limited cleavage was observed when the ratio of active enzyme (PmC11:PmC11C179A) was increased to ∼1:10 and 1:4, with complete cleavage observed at a ratio of 1:1 (Fig. 2E). RESULTS
119 124 PmC11 protein These studies revealed that there was no apparent cleavage of PmC11C179A by the active enzyme at low concentrations of PmC11 and that only limited cleavage was observed when the ratio of active enzyme (PmC11:PmC11C179A) was increased to ∼1:10 and 1:4, with complete cleavage observed at a ratio of 1:1 (Fig. 2E). RESULTS
187 193 active protein_state These studies revealed that there was no apparent cleavage of PmC11C179A by the active enzyme at low concentrations of PmC11 and that only limited cleavage was observed when the ratio of active enzyme (PmC11:PmC11C179A) was increased to ∼1:10 and 1:4, with complete cleavage observed at a ratio of 1:1 (Fig. 2E). RESULTS
202 207 PmC11 protein These studies revealed that there was no apparent cleavage of PmC11C179A by the active enzyme at low concentrations of PmC11 and that only limited cleavage was observed when the ratio of active enzyme (PmC11:PmC11C179A) was increased to ∼1:10 and 1:4, with complete cleavage observed at a ratio of 1:1 (Fig. 2E). RESULTS
208 218 PmC11C179A mutant These studies revealed that there was no apparent cleavage of PmC11C179A by the active enzyme at low concentrations of PmC11 and that only limited cleavage was observed when the ratio of active enzyme (PmC11:PmC11C179A) was increased to ∼1:10 and 1:4, with complete cleavage observed at a ratio of 1:1 (Fig. 2E). RESULTS
224 250 increased to ∼1:10 and 1:4 experimental_method These studies revealed that there was no apparent cleavage of PmC11C179A by the active enzyme at low concentrations of PmC11 and that only limited cleavage was observed when the ratio of active enzyme (PmC11:PmC11C179A) was increased to ∼1:10 and 1:4, with complete cleavage observed at a ratio of 1:1 (Fig. 2E). RESULTS
289 301 ratio of 1:1 experimental_method These studies revealed that there was no apparent cleavage of PmC11C179A by the active enzyme at low concentrations of PmC11 and that only limited cleavage was observed when the ratio of active enzyme (PmC11:PmC11C179A) was increased to ∼1:10 and 1:4, with complete cleavage observed at a ratio of 1:1 (Fig. 2E). RESULTS
19 27 cleavage ptm This suggests that cleavage of PmC11C179A was most likely an effect of the increasing concentration of PmC11 and intermolecular cleavage. RESULTS
31 41 PmC11C179A mutant This suggests that cleavage of PmC11C179A was most likely an effect of the increasing concentration of PmC11 and intermolecular cleavage. RESULTS
103 108 PmC11 protein This suggests that cleavage of PmC11C179A was most likely an effect of the increasing concentration of PmC11 and intermolecular cleavage. RESULTS
42 50 pro-form protein_state Collectively, these data suggest that the pro-form of PmC11 is autoinhibited by a section of L5 blocking access to the active site, prior to intramolecular cleavage at Lys147. RESULTS
54 59 PmC11 protein Collectively, these data suggest that the pro-form of PmC11 is autoinhibited by a section of L5 blocking access to the active site, prior to intramolecular cleavage at Lys147. RESULTS
63 76 autoinhibited protein_state Collectively, these data suggest that the pro-form of PmC11 is autoinhibited by a section of L5 blocking access to the active site, prior to intramolecular cleavage at Lys147. RESULTS
93 95 L5 structure_element Collectively, these data suggest that the pro-form of PmC11 is autoinhibited by a section of L5 blocking access to the active site, prior to intramolecular cleavage at Lys147. RESULTS
119 130 active site site Collectively, these data suggest that the pro-form of PmC11 is autoinhibited by a section of L5 blocking access to the active site, prior to intramolecular cleavage at Lys147. RESULTS
141 164 intramolecular cleavage ptm Collectively, these data suggest that the pro-form of PmC11 is autoinhibited by a section of L5 blocking access to the active site, prior to intramolecular cleavage at Lys147. RESULTS
168 174 Lys147 residue_name_number Collectively, these data suggest that the pro-form of PmC11 is autoinhibited by a section of L5 blocking access to the active site, prior to intramolecular cleavage at Lys147. RESULTS
5 13 cleavage ptm This cleavage subsequently allows movement of the region containing Lys147 and the active site to open up for substrate access. RESULTS
68 74 Lys147 residue_name_number This cleavage subsequently allows movement of the region containing Lys147 and the active site to open up for substrate access. RESULTS
83 94 active site site This cleavage subsequently allows movement of the region containing Lys147 and the active site to open up for substrate access. RESULTS
98 102 open protein_state This cleavage subsequently allows movement of the region containing Lys147 and the active site to open up for substrate access. RESULTS
25 30 PmC11 protein Substrate Specificity of PmC11 RESULTS
4 26 autocatalytic cleavage ptm The autocatalytic cleavage of PmC11 at Lys147 (sequence KLK∧A) demonstrates that the enzyme accepts substrates with Lys in the P1 position. RESULTS
30 35 PmC11 protein The autocatalytic cleavage of PmC11 at Lys147 (sequence KLK∧A) demonstrates that the enzyme accepts substrates with Lys in the P1 position. RESULTS
39 45 Lys147 residue_name_number The autocatalytic cleavage of PmC11 at Lys147 (sequence KLK∧A) demonstrates that the enzyme accepts substrates with Lys in the P1 position. RESULTS
116 119 Lys residue_name The autocatalytic cleavage of PmC11 at Lys147 (sequence KLK∧A) demonstrates that the enzyme accepts substrates with Lys in the P1 position. RESULTS
127 129 P1 residue_number The autocatalytic cleavage of PmC11 at Lys147 (sequence KLK∧A) demonstrates that the enzyme accepts substrates with Lys in the P1 position. RESULTS
13 18 PmC11 protein As expected, PmC11 showed no activity against substrates with Pro or Asp in P1 but was active toward substrates with a basic residue in P1 such as Bz-R-AMC, Z-GGR-AMC, and BOC-VLK-AMC. RESULTS
62 65 Pro residue_name As expected, PmC11 showed no activity against substrates with Pro or Asp in P1 but was active toward substrates with a basic residue in P1 such as Bz-R-AMC, Z-GGR-AMC, and BOC-VLK-AMC. RESULTS
69 72 Asp residue_name As expected, PmC11 showed no activity against substrates with Pro or Asp in P1 but was active toward substrates with a basic residue in P1 such as Bz-R-AMC, Z-GGR-AMC, and BOC-VLK-AMC. RESULTS
76 78 P1 residue_number As expected, PmC11 showed no activity against substrates with Pro or Asp in P1 but was active toward substrates with a basic residue in P1 such as Bz-R-AMC, Z-GGR-AMC, and BOC-VLK-AMC. RESULTS
87 93 active protein_state As expected, PmC11 showed no activity against substrates with Pro or Asp in P1 but was active toward substrates with a basic residue in P1 such as Bz-R-AMC, Z-GGR-AMC, and BOC-VLK-AMC. RESULTS
136 138 P1 residue_number As expected, PmC11 showed no activity against substrates with Pro or Asp in P1 but was active toward substrates with a basic residue in P1 such as Bz-R-AMC, Z-GGR-AMC, and BOC-VLK-AMC. RESULTS
147 155 Bz-R-AMC chemical As expected, PmC11 showed no activity against substrates with Pro or Asp in P1 but was active toward substrates with a basic residue in P1 such as Bz-R-AMC, Z-GGR-AMC, and BOC-VLK-AMC. RESULTS
157 166 Z-GGR-AMC chemical As expected, PmC11 showed no activity against substrates with Pro or Asp in P1 but was active toward substrates with a basic residue in P1 such as Bz-R-AMC, Z-GGR-AMC, and BOC-VLK-AMC. RESULTS
172 183 BOC-VLK-AMC chemical As expected, PmC11 showed no activity against substrates with Pro or Asp in P1 but was active toward substrates with a basic residue in P1 such as Bz-R-AMC, Z-GGR-AMC, and BOC-VLK-AMC. RESULTS
59 62 Arg residue_name The rate of cleavage was ∼3-fold greater toward the single Arg substrate Bz-R-AMC than for the other two (Fig. 2F) and, unexpectedly, PmC11 showed no activity toward BOC-K-AMC. RESULTS
73 81 Bz-R-AMC chemical The rate of cleavage was ∼3-fold greater toward the single Arg substrate Bz-R-AMC than for the other two (Fig. 2F) and, unexpectedly, PmC11 showed no activity toward BOC-K-AMC. RESULTS
134 139 PmC11 protein The rate of cleavage was ∼3-fold greater toward the single Arg substrate Bz-R-AMC than for the other two (Fig. 2F) and, unexpectedly, PmC11 showed no activity toward BOC-K-AMC. RESULTS
166 175 BOC-K-AMC chemical The rate of cleavage was ∼3-fold greater toward the single Arg substrate Bz-R-AMC than for the other two (Fig. 2F) and, unexpectedly, PmC11 showed no activity toward BOC-K-AMC. RESULTS
27 32 PmC11 protein These results confirm that PmC11 accepts substrates containing Arg or Lys in P1 with a possible preference for Arg. RESULTS
63 66 Arg residue_name These results confirm that PmC11 accepts substrates containing Arg or Lys in P1 with a possible preference for Arg. RESULTS
70 73 Lys residue_name These results confirm that PmC11 accepts substrates containing Arg or Lys in P1 with a possible preference for Arg. RESULTS
77 79 P1 residue_number These results confirm that PmC11 accepts substrates containing Arg or Lys in P1 with a possible preference for Arg. RESULTS
111 114 Arg residue_name These results confirm that PmC11 accepts substrates containing Arg or Lys in P1 with a possible preference for Arg. RESULTS
4 18 catalytic dyad site The catalytic dyad of PmC11 sits near the bottom of an open pocket on the surface of the enzyme at a conserved location in the clan CD family. RESULTS
22 27 PmC11 protein The catalytic dyad of PmC11 sits near the bottom of an open pocket on the surface of the enzyme at a conserved location in the clan CD family. RESULTS
55 59 open protein_state The catalytic dyad of PmC11 sits near the bottom of an open pocket on the surface of the enzyme at a conserved location in the clan CD family. RESULTS
60 66 pocket site The catalytic dyad of PmC11 sits near the bottom of an open pocket on the surface of the enzyme at a conserved location in the clan CD family. RESULTS
101 119 conserved location protein_state The catalytic dyad of PmC11 sits near the bottom of an open pocket on the surface of the enzyme at a conserved location in the clan CD family. RESULTS
132 141 CD family protein_type The catalytic dyad of PmC11 sits near the bottom of an open pocket on the surface of the enzyme at a conserved location in the clan CD family. RESULTS
4 9 PmC11 protein The PmC11 structure reveals that the catalytic dyad forms part of a large acidic pocket (Fig. 2G), consistent with a binding site for a basic substrate. RESULTS
10 19 structure evidence The PmC11 structure reveals that the catalytic dyad forms part of a large acidic pocket (Fig. 2G), consistent with a binding site for a basic substrate. RESULTS
37 51 catalytic dyad site The PmC11 structure reveals that the catalytic dyad forms part of a large acidic pocket (Fig. 2G), consistent with a binding site for a basic substrate. RESULTS
74 87 acidic pocket site The PmC11 structure reveals that the catalytic dyad forms part of a large acidic pocket (Fig. 2G), consistent with a binding site for a basic substrate. RESULTS
117 129 binding site site The PmC11 structure reveals that the catalytic dyad forms part of a large acidic pocket (Fig. 2G), consistent with a binding site for a basic substrate. RESULTS
5 11 pocket site This pocket is lined with the potential functional side chains of Asn50, Asp177, and Thr204 with Gly134, Asp207, and Met205 also contributing to the pocket (Fig. 2A). RESULTS
66 71 Asn50 residue_name_number This pocket is lined with the potential functional side chains of Asn50, Asp177, and Thr204 with Gly134, Asp207, and Met205 also contributing to the pocket (Fig. 2A). RESULTS
73 79 Asp177 residue_name_number This pocket is lined with the potential functional side chains of Asn50, Asp177, and Thr204 with Gly134, Asp207, and Met205 also contributing to the pocket (Fig. 2A). RESULTS
85 91 Thr204 residue_name_number This pocket is lined with the potential functional side chains of Asn50, Asp177, and Thr204 with Gly134, Asp207, and Met205 also contributing to the pocket (Fig. 2A). RESULTS
97 103 Gly134 residue_name_number This pocket is lined with the potential functional side chains of Asn50, Asp177, and Thr204 with Gly134, Asp207, and Met205 also contributing to the pocket (Fig. 2A). RESULTS
105 111 Asp207 residue_name_number This pocket is lined with the potential functional side chains of Asn50, Asp177, and Thr204 with Gly134, Asp207, and Met205 also contributing to the pocket (Fig. 2A). RESULTS
117 123 Met205 residue_name_number This pocket is lined with the potential functional side chains of Asn50, Asp177, and Thr204 with Gly134, Asp207, and Met205 also contributing to the pocket (Fig. 2A). RESULTS
149 155 pocket site This pocket is lined with the potential functional side chains of Asn50, Asp177, and Thr204 with Gly134, Asp207, and Met205 also contributing to the pocket (Fig. 2A). RESULTS
54 74 structurally similar protein_state Interestingly, these residues are in regions that are structurally similar to those involved in the S1 binding pockets of other clan CD members (shown in Ref.). RESULTS
100 118 S1 binding pockets site Interestingly, these residues are in regions that are structurally similar to those involved in the S1 binding pockets of other clan CD members (shown in Ref.). RESULTS
128 143 clan CD members protein_type Interestingly, these residues are in regions that are structurally similar to those involved in the S1 binding pockets of other clan CD members (shown in Ref.). RESULTS
8 13 PmC11 protein Because PmC11 recognizes basic substrates, the tetrapeptide inhibitor Z-VRPR-FMK was tested as an enzyme inhibitor and was found to inhibit both the autoprocessing and activity of PmC11 (Fig. 3A). RESULTS
70 80 Z-VRPR-FMK chemical Because PmC11 recognizes basic substrates, the tetrapeptide inhibitor Z-VRPR-FMK was tested as an enzyme inhibitor and was found to inhibit both the autoprocessing and activity of PmC11 (Fig. 3A). RESULTS
132 139 inhibit protein_state Because PmC11 recognizes basic substrates, the tetrapeptide inhibitor Z-VRPR-FMK was tested as an enzyme inhibitor and was found to inhibit both the autoprocessing and activity of PmC11 (Fig. 3A). RESULTS
149 163 autoprocessing ptm Because PmC11 recognizes basic substrates, the tetrapeptide inhibitor Z-VRPR-FMK was tested as an enzyme inhibitor and was found to inhibit both the autoprocessing and activity of PmC11 (Fig. 3A). RESULTS
180 185 PmC11 protein Because PmC11 recognizes basic substrates, the tetrapeptide inhibitor Z-VRPR-FMK was tested as an enzyme inhibitor and was found to inhibit both the autoprocessing and activity of PmC11 (Fig. 3A). RESULTS
0 10 Z-VRPR-FMK chemical Z-VRPR-FMK was also shown to bind to the enzyme: a size-shift was observed, by SDS-PAGE analysis, in the larger processed product of PmC11 suggesting that the inhibitor bound to the active site (Fig. 3B). RESULTS
51 61 size-shift evidence Z-VRPR-FMK was also shown to bind to the enzyme: a size-shift was observed, by SDS-PAGE analysis, in the larger processed product of PmC11 suggesting that the inhibitor bound to the active site (Fig. 3B). RESULTS
79 87 SDS-PAGE experimental_method Z-VRPR-FMK was also shown to bind to the enzyme: a size-shift was observed, by SDS-PAGE analysis, in the larger processed product of PmC11 suggesting that the inhibitor bound to the active site (Fig. 3B). RESULTS
133 138 PmC11 protein Z-VRPR-FMK was also shown to bind to the enzyme: a size-shift was observed, by SDS-PAGE analysis, in the larger processed product of PmC11 suggesting that the inhibitor bound to the active site (Fig. 3B). RESULTS
159 174 inhibitor bound protein_state Z-VRPR-FMK was also shown to bind to the enzyme: a size-shift was observed, by SDS-PAGE analysis, in the larger processed product of PmC11 suggesting that the inhibitor bound to the active site (Fig. 3B). RESULTS
182 193 active site site Z-VRPR-FMK was also shown to bind to the enzyme: a size-shift was observed, by SDS-PAGE analysis, in the larger processed product of PmC11 suggesting that the inhibitor bound to the active site (Fig. 3B). RESULTS
2 19 structure overlay experimental_method A structure overlay of PmC11 with the MALT1-paracacaspase (MALT1-P), in complex with Z-VRPR-FMK, revealed that the PmC11 dyad sits in a very similar position to that of active MALT1-P and that Asn50, Asp177, and Asp207 superimpose well with the principal MALT1-P inhibitor binding residues (Asp365, Asp462, and Glu500, respectively (VRPR-FMK from MALT1-P with the corresponding PmC11 residues from the structural overlay is shown in Fig. 1D), as described in Ref.). RESULTS
23 28 PmC11 protein A structure overlay of PmC11 with the MALT1-paracacaspase (MALT1-P), in complex with Z-VRPR-FMK, revealed that the PmC11 dyad sits in a very similar position to that of active MALT1-P and that Asn50, Asp177, and Asp207 superimpose well with the principal MALT1-P inhibitor binding residues (Asp365, Asp462, and Glu500, respectively (VRPR-FMK from MALT1-P with the corresponding PmC11 residues from the structural overlay is shown in Fig. 1D), as described in Ref.). RESULTS
38 57 MALT1-paracacaspase protein A structure overlay of PmC11 with the MALT1-paracacaspase (MALT1-P), in complex with Z-VRPR-FMK, revealed that the PmC11 dyad sits in a very similar position to that of active MALT1-P and that Asn50, Asp177, and Asp207 superimpose well with the principal MALT1-P inhibitor binding residues (Asp365, Asp462, and Glu500, respectively (VRPR-FMK from MALT1-P with the corresponding PmC11 residues from the structural overlay is shown in Fig. 1D), as described in Ref.). RESULTS
59 66 MALT1-P protein A structure overlay of PmC11 with the MALT1-paracacaspase (MALT1-P), in complex with Z-VRPR-FMK, revealed that the PmC11 dyad sits in a very similar position to that of active MALT1-P and that Asn50, Asp177, and Asp207 superimpose well with the principal MALT1-P inhibitor binding residues (Asp365, Asp462, and Glu500, respectively (VRPR-FMK from MALT1-P with the corresponding PmC11 residues from the structural overlay is shown in Fig. 1D), as described in Ref.). RESULTS
72 79 complex protein_state A structure overlay of PmC11 with the MALT1-paracacaspase (MALT1-P), in complex with Z-VRPR-FMK, revealed that the PmC11 dyad sits in a very similar position to that of active MALT1-P and that Asn50, Asp177, and Asp207 superimpose well with the principal MALT1-P inhibitor binding residues (Asp365, Asp462, and Glu500, respectively (VRPR-FMK from MALT1-P with the corresponding PmC11 residues from the structural overlay is shown in Fig. 1D), as described in Ref.). RESULTS
85 95 Z-VRPR-FMK chemical A structure overlay of PmC11 with the MALT1-paracacaspase (MALT1-P), in complex with Z-VRPR-FMK, revealed that the PmC11 dyad sits in a very similar position to that of active MALT1-P and that Asn50, Asp177, and Asp207 superimpose well with the principal MALT1-P inhibitor binding residues (Asp365, Asp462, and Glu500, respectively (VRPR-FMK from MALT1-P with the corresponding PmC11 residues from the structural overlay is shown in Fig. 1D), as described in Ref.). RESULTS
115 120 PmC11 protein A structure overlay of PmC11 with the MALT1-paracacaspase (MALT1-P), in complex with Z-VRPR-FMK, revealed that the PmC11 dyad sits in a very similar position to that of active MALT1-P and that Asn50, Asp177, and Asp207 superimpose well with the principal MALT1-P inhibitor binding residues (Asp365, Asp462, and Glu500, respectively (VRPR-FMK from MALT1-P with the corresponding PmC11 residues from the structural overlay is shown in Fig. 1D), as described in Ref.). RESULTS
121 125 dyad site A structure overlay of PmC11 with the MALT1-paracacaspase (MALT1-P), in complex with Z-VRPR-FMK, revealed that the PmC11 dyad sits in a very similar position to that of active MALT1-P and that Asn50, Asp177, and Asp207 superimpose well with the principal MALT1-P inhibitor binding residues (Asp365, Asp462, and Glu500, respectively (VRPR-FMK from MALT1-P with the corresponding PmC11 residues from the structural overlay is shown in Fig. 1D), as described in Ref.). RESULTS
169 175 active protein_state A structure overlay of PmC11 with the MALT1-paracacaspase (MALT1-P), in complex with Z-VRPR-FMK, revealed that the PmC11 dyad sits in a very similar position to that of active MALT1-P and that Asn50, Asp177, and Asp207 superimpose well with the principal MALT1-P inhibitor binding residues (Asp365, Asp462, and Glu500, respectively (VRPR-FMK from MALT1-P with the corresponding PmC11 residues from the structural overlay is shown in Fig. 1D), as described in Ref.). RESULTS
176 183 MALT1-P protein A structure overlay of PmC11 with the MALT1-paracacaspase (MALT1-P), in complex with Z-VRPR-FMK, revealed that the PmC11 dyad sits in a very similar position to that of active MALT1-P and that Asn50, Asp177, and Asp207 superimpose well with the principal MALT1-P inhibitor binding residues (Asp365, Asp462, and Glu500, respectively (VRPR-FMK from MALT1-P with the corresponding PmC11 residues from the structural overlay is shown in Fig. 1D), as described in Ref.). RESULTS
193 198 Asn50 residue_name_number A structure overlay of PmC11 with the MALT1-paracacaspase (MALT1-P), in complex with Z-VRPR-FMK, revealed that the PmC11 dyad sits in a very similar position to that of active MALT1-P and that Asn50, Asp177, and Asp207 superimpose well with the principal MALT1-P inhibitor binding residues (Asp365, Asp462, and Glu500, respectively (VRPR-FMK from MALT1-P with the corresponding PmC11 residues from the structural overlay is shown in Fig. 1D), as described in Ref.). RESULTS
200 206 Asp177 residue_name_number A structure overlay of PmC11 with the MALT1-paracacaspase (MALT1-P), in complex with Z-VRPR-FMK, revealed that the PmC11 dyad sits in a very similar position to that of active MALT1-P and that Asn50, Asp177, and Asp207 superimpose well with the principal MALT1-P inhibitor binding residues (Asp365, Asp462, and Glu500, respectively (VRPR-FMK from MALT1-P with the corresponding PmC11 residues from the structural overlay is shown in Fig. 1D), as described in Ref.). RESULTS
212 218 Asp207 residue_name_number A structure overlay of PmC11 with the MALT1-paracacaspase (MALT1-P), in complex with Z-VRPR-FMK, revealed that the PmC11 dyad sits in a very similar position to that of active MALT1-P and that Asn50, Asp177, and Asp207 superimpose well with the principal MALT1-P inhibitor binding residues (Asp365, Asp462, and Glu500, respectively (VRPR-FMK from MALT1-P with the corresponding PmC11 residues from the structural overlay is shown in Fig. 1D), as described in Ref.). RESULTS
255 262 MALT1-P protein A structure overlay of PmC11 with the MALT1-paracacaspase (MALT1-P), in complex with Z-VRPR-FMK, revealed that the PmC11 dyad sits in a very similar position to that of active MALT1-P and that Asn50, Asp177, and Asp207 superimpose well with the principal MALT1-P inhibitor binding residues (Asp365, Asp462, and Glu500, respectively (VRPR-FMK from MALT1-P with the corresponding PmC11 residues from the structural overlay is shown in Fig. 1D), as described in Ref.). RESULTS
263 289 inhibitor binding residues site A structure overlay of PmC11 with the MALT1-paracacaspase (MALT1-P), in complex with Z-VRPR-FMK, revealed that the PmC11 dyad sits in a very similar position to that of active MALT1-P and that Asn50, Asp177, and Asp207 superimpose well with the principal MALT1-P inhibitor binding residues (Asp365, Asp462, and Glu500, respectively (VRPR-FMK from MALT1-P with the corresponding PmC11 residues from the structural overlay is shown in Fig. 1D), as described in Ref.). RESULTS
291 297 Asp365 residue_name_number A structure overlay of PmC11 with the MALT1-paracacaspase (MALT1-P), in complex with Z-VRPR-FMK, revealed that the PmC11 dyad sits in a very similar position to that of active MALT1-P and that Asn50, Asp177, and Asp207 superimpose well with the principal MALT1-P inhibitor binding residues (Asp365, Asp462, and Glu500, respectively (VRPR-FMK from MALT1-P with the corresponding PmC11 residues from the structural overlay is shown in Fig. 1D), as described in Ref.). RESULTS
299 305 Asp462 residue_name_number A structure overlay of PmC11 with the MALT1-paracacaspase (MALT1-P), in complex with Z-VRPR-FMK, revealed that the PmC11 dyad sits in a very similar position to that of active MALT1-P and that Asn50, Asp177, and Asp207 superimpose well with the principal MALT1-P inhibitor binding residues (Asp365, Asp462, and Glu500, respectively (VRPR-FMK from MALT1-P with the corresponding PmC11 residues from the structural overlay is shown in Fig. 1D), as described in Ref.). RESULTS
311 317 Glu500 residue_name_number A structure overlay of PmC11 with the MALT1-paracacaspase (MALT1-P), in complex with Z-VRPR-FMK, revealed that the PmC11 dyad sits in a very similar position to that of active MALT1-P and that Asn50, Asp177, and Asp207 superimpose well with the principal MALT1-P inhibitor binding residues (Asp365, Asp462, and Glu500, respectively (VRPR-FMK from MALT1-P with the corresponding PmC11 residues from the structural overlay is shown in Fig. 1D), as described in Ref.). RESULTS
333 341 VRPR-FMK chemical A structure overlay of PmC11 with the MALT1-paracacaspase (MALT1-P), in complex with Z-VRPR-FMK, revealed that the PmC11 dyad sits in a very similar position to that of active MALT1-P and that Asn50, Asp177, and Asp207 superimpose well with the principal MALT1-P inhibitor binding residues (Asp365, Asp462, and Glu500, respectively (VRPR-FMK from MALT1-P with the corresponding PmC11 residues from the structural overlay is shown in Fig. 1D), as described in Ref.). RESULTS
347 354 MALT1-P protein A structure overlay of PmC11 with the MALT1-paracacaspase (MALT1-P), in complex with Z-VRPR-FMK, revealed that the PmC11 dyad sits in a very similar position to that of active MALT1-P and that Asn50, Asp177, and Asp207 superimpose well with the principal MALT1-P inhibitor binding residues (Asp365, Asp462, and Glu500, respectively (VRPR-FMK from MALT1-P with the corresponding PmC11 residues from the structural overlay is shown in Fig. 1D), as described in Ref.). RESULTS
378 383 PmC11 protein A structure overlay of PmC11 with the MALT1-paracacaspase (MALT1-P), in complex with Z-VRPR-FMK, revealed that the PmC11 dyad sits in a very similar position to that of active MALT1-P and that Asn50, Asp177, and Asp207 superimpose well with the principal MALT1-P inhibitor binding residues (Asp365, Asp462, and Glu500, respectively (VRPR-FMK from MALT1-P with the corresponding PmC11 residues from the structural overlay is shown in Fig. 1D), as described in Ref.). RESULTS
402 420 structural overlay experimental_method A structure overlay of PmC11 with the MALT1-paracacaspase (MALT1-P), in complex with Z-VRPR-FMK, revealed that the PmC11 dyad sits in a very similar position to that of active MALT1-P and that Asn50, Asp177, and Asp207 superimpose well with the principal MALT1-P inhibitor binding residues (Asp365, Asp462, and Glu500, respectively (VRPR-FMK from MALT1-P with the corresponding PmC11 residues from the structural overlay is shown in Fig. 1D), as described in Ref.). RESULTS
0 6 Asp177 residue_name_number Asp177 is located near the catalytic cysteine and is conserved throughout the C11 family, suggesting it is the primary S1 binding site residue. RESULTS
27 36 catalytic protein_state Asp177 is located near the catalytic cysteine and is conserved throughout the C11 family, suggesting it is the primary S1 binding site residue. RESULTS
37 45 cysteine residue_name Asp177 is located near the catalytic cysteine and is conserved throughout the C11 family, suggesting it is the primary S1 binding site residue. RESULTS
53 73 conserved throughout protein_state Asp177 is located near the catalytic cysteine and is conserved throughout the C11 family, suggesting it is the primary S1 binding site residue. RESULTS
78 88 C11 family protein_type Asp177 is located near the catalytic cysteine and is conserved throughout the C11 family, suggesting it is the primary S1 binding site residue. RESULTS
119 142 S1 binding site residue site Asp177 is located near the catalytic cysteine and is conserved throughout the C11 family, suggesting it is the primary S1 binding site residue. RESULTS
7 16 structure evidence In the structure of PmC11, Asp207 resides on a flexible loop pointing away from the S1 binding pocket (Fig. 3C). RESULTS
20 25 PmC11 protein In the structure of PmC11, Asp207 resides on a flexible loop pointing away from the S1 binding pocket (Fig. 3C). RESULTS
27 33 Asp207 residue_name_number In the structure of PmC11, Asp207 resides on a flexible loop pointing away from the S1 binding pocket (Fig. 3C). RESULTS
56 60 loop structure_element In the structure of PmC11, Asp207 resides on a flexible loop pointing away from the S1 binding pocket (Fig. 3C). RESULTS
84 101 S1 binding pocket site In the structure of PmC11, Asp207 resides on a flexible loop pointing away from the S1 binding pocket (Fig. 3C). RESULTS
14 18 loop structure_element However, this loop has been shown to be important for substrate binding in clan CD and this residue could easily rotate and be involved in substrate binding in PmC11. RESULTS
75 82 clan CD protein_type However, this loop has been shown to be important for substrate binding in clan CD and this residue could easily rotate and be involved in substrate binding in PmC11. RESULTS
160 165 PmC11 protein However, this loop has been shown to be important for substrate binding in clan CD and this residue could easily rotate and be involved in substrate binding in PmC11. RESULTS
6 11 Asn50 residue_name_number Thus, Asn50, Asp177, and Asp207 are most likely responsible for the substrate specificity of PmC11. RESULTS
13 19 Asp177 residue_name_number Thus, Asn50, Asp177, and Asp207 are most likely responsible for the substrate specificity of PmC11. RESULTS
25 31 Asp207 residue_name_number Thus, Asn50, Asp177, and Asp207 are most likely responsible for the substrate specificity of PmC11. RESULTS
93 98 PmC11 protein Thus, Asn50, Asp177, and Asp207 are most likely responsible for the substrate specificity of PmC11. RESULTS
0 6 Asp177 residue_name_number Asp177 is highly conserved throughout the clan CD C11 peptidases and is thought to be primarily responsible for substrate specificity of the clan CD enzymes, as also illustrated from the proximity of these residues relative to the inhibitor Z-VRPR-FMK when PmC11 is overlaid on the MALT1-P structure (Fig. 3C). RESULTS
10 26 highly conserved protein_state Asp177 is highly conserved throughout the clan CD C11 peptidases and is thought to be primarily responsible for substrate specificity of the clan CD enzymes, as also illustrated from the proximity of these residues relative to the inhibitor Z-VRPR-FMK when PmC11 is overlaid on the MALT1-P structure (Fig. 3C). RESULTS
42 64 clan CD C11 peptidases protein_type Asp177 is highly conserved throughout the clan CD C11 peptidases and is thought to be primarily responsible for substrate specificity of the clan CD enzymes, as also illustrated from the proximity of these residues relative to the inhibitor Z-VRPR-FMK when PmC11 is overlaid on the MALT1-P structure (Fig. 3C). RESULTS
141 156 clan CD enzymes protein_type Asp177 is highly conserved throughout the clan CD C11 peptidases and is thought to be primarily responsible for substrate specificity of the clan CD enzymes, as also illustrated from the proximity of these residues relative to the inhibitor Z-VRPR-FMK when PmC11 is overlaid on the MALT1-P structure (Fig. 3C). RESULTS
241 251 Z-VRPR-FMK chemical Asp177 is highly conserved throughout the clan CD C11 peptidases and is thought to be primarily responsible for substrate specificity of the clan CD enzymes, as also illustrated from the proximity of these residues relative to the inhibitor Z-VRPR-FMK when PmC11 is overlaid on the MALT1-P structure (Fig. 3C). RESULTS
257 262 PmC11 protein Asp177 is highly conserved throughout the clan CD C11 peptidases and is thought to be primarily responsible for substrate specificity of the clan CD enzymes, as also illustrated from the proximity of these residues relative to the inhibitor Z-VRPR-FMK when PmC11 is overlaid on the MALT1-P structure (Fig. 3C). RESULTS
266 274 overlaid experimental_method Asp177 is highly conserved throughout the clan CD C11 peptidases and is thought to be primarily responsible for substrate specificity of the clan CD enzymes, as also illustrated from the proximity of these residues relative to the inhibitor Z-VRPR-FMK when PmC11 is overlaid on the MALT1-P structure (Fig. 3C). RESULTS
282 289 MALT1-P protein Asp177 is highly conserved throughout the clan CD C11 peptidases and is thought to be primarily responsible for substrate specificity of the clan CD enzymes, as also illustrated from the proximity of these residues relative to the inhibitor Z-VRPR-FMK when PmC11 is overlaid on the MALT1-P structure (Fig. 3C). RESULTS
290 299 structure evidence Asp177 is highly conserved throughout the clan CD C11 peptidases and is thought to be primarily responsible for substrate specificity of the clan CD enzymes, as also illustrated from the proximity of these residues relative to the inhibitor Z-VRPR-FMK when PmC11 is overlaid on the MALT1-P structure (Fig. 3C). RESULTS
0 5 PmC11 protein PmC11 binds and is inhibited by Z-VRPR-FMK and does not require Ca2+ for activity. FIG
32 42 Z-VRPR-FMK chemical PmC11 binds and is inhibited by Z-VRPR-FMK and does not require Ca2+ for activity. FIG
64 68 Ca2+ chemical PmC11 binds and is inhibited by Z-VRPR-FMK and does not require Ca2+ for activity. FIG
35 45 Z-VRPR-FMK chemical A, PmC11 activity is inhibited by Z-VRPR-FMK. FIG
12 20 Bz-R-AMC chemical Cleavage of Bz-R-AMC by PmC11 was measured in a fluorometric activity assay with (+, purple) and without (−, red) Z-VRPR-FMK. FIG
24 29 PmC11 protein Cleavage of Bz-R-AMC by PmC11 was measured in a fluorometric activity assay with (+, purple) and without (−, red) Z-VRPR-FMK. FIG
48 75 fluorometric activity assay experimental_method Cleavage of Bz-R-AMC by PmC11 was measured in a fluorometric activity assay with (+, purple) and without (−, red) Z-VRPR-FMK. FIG
114 124 Z-VRPR-FMK chemical Cleavage of Bz-R-AMC by PmC11 was measured in a fluorometric activity assay with (+, purple) and without (−, red) Z-VRPR-FMK. FIG
3 18 gel-shift assay experimental_method B, gel-shift assay reveals that Z-VRPR-FMK binds to PmC11. FIG
32 42 Z-VRPR-FMK chemical B, gel-shift assay reveals that Z-VRPR-FMK binds to PmC11. FIG
52 57 PmC11 protein B, gel-shift assay reveals that Z-VRPR-FMK binds to PmC11. FIG
10 19 incubated experimental_method PmC11 was incubated with (+) or without (−) Z-VRPR-FMK and the samples analyzed on a 10% SDS-PAGE gel. FIG
44 54 Z-VRPR-FMK chemical PmC11 was incubated with (+) or without (−) Z-VRPR-FMK and the samples analyzed on a 10% SDS-PAGE gel. FIG
89 97 SDS-PAGE experimental_method PmC11 was incubated with (+) or without (−) Z-VRPR-FMK and the samples analyzed on a 10% SDS-PAGE gel. FIG
2 12 size shift evidence A size shift can be observed in the larger processed product of PmC11 (26.1 kDa). FIG
64 69 PmC11 protein A size shift can be observed in the larger processed product of PmC11 (26.1 kDa). FIG
3 8 PmC11 protein C, PmC11 with the Z-VRPR-FMK from the MALT1-paracacaspase (MALT1-P) superimposed. FIG
18 28 Z-VRPR-FMK chemical C, PmC11 with the Z-VRPR-FMK from the MALT1-paracacaspase (MALT1-P) superimposed. FIG
38 57 MALT1-paracacaspase protein C, PmC11 with the Z-VRPR-FMK from the MALT1-paracacaspase (MALT1-P) superimposed. FIG
59 66 MALT1-P protein C, PmC11 with the Z-VRPR-FMK from the MALT1-paracacaspase (MALT1-P) superimposed. FIG
68 80 superimposed experimental_method C, PmC11 with the Z-VRPR-FMK from the MALT1-paracacaspase (MALT1-P) superimposed. FIG
2 38 three-dimensional structural overlay experimental_method A three-dimensional structural overlay of Z-VRPR-FMK from the MALT1-P complex onto PmC11. FIG
42 52 Z-VRPR-FMK chemical A three-dimensional structural overlay of Z-VRPR-FMK from the MALT1-P complex onto PmC11. FIG
62 69 MALT1-P protein A three-dimensional structural overlay of Z-VRPR-FMK from the MALT1-P complex onto PmC11. FIG
83 88 PmC11 protein A three-dimensional structural overlay of Z-VRPR-FMK from the MALT1-P complex onto PmC11. FIG
32 42 Z-VRPR-FMK chemical The position and orientation of Z-VRPR-FMK was taken from superposition of the PmC11 and MALTI_P structures and indicates the presumed active site of PmC11. FIG
58 71 superposition experimental_method The position and orientation of Z-VRPR-FMK was taken from superposition of the PmC11 and MALTI_P structures and indicates the presumed active site of PmC11. FIG
79 84 PmC11 protein The position and orientation of Z-VRPR-FMK was taken from superposition of the PmC11 and MALTI_P structures and indicates the presumed active site of PmC11. FIG
89 96 MALTI_P protein The position and orientation of Z-VRPR-FMK was taken from superposition of the PmC11 and MALTI_P structures and indicates the presumed active site of PmC11. FIG
97 107 structures evidence The position and orientation of Z-VRPR-FMK was taken from superposition of the PmC11 and MALTI_P structures and indicates the presumed active site of PmC11. FIG
135 146 active site site The position and orientation of Z-VRPR-FMK was taken from superposition of the PmC11 and MALTI_P structures and indicates the presumed active site of PmC11. FIG
150 155 PmC11 protein The position and orientation of Z-VRPR-FMK was taken from superposition of the PmC11 and MALTI_P structures and indicates the presumed active site of PmC11. FIG
83 104 binding site residues site Residues surrounding the inhibitor are labeled and represent potentially important binding site residues, labeled in black and shown in an atomic representation. FIG
52 57 PmC11 protein C, divalent cations do not increase the activity of PmC11. FIG
16 24 Bz-R-AMC chemical The cleavage of Bz-R-AMC by PmC11 was measured in the presence of the cations Ca2+, Mn2+, Zn2+, Co2+, Cu2+, Mg2+, and Fe3+ with EGTA as a negative control, and relative fluorescence measured against time (min). FIG
28 33 PmC11 protein The cleavage of Bz-R-AMC by PmC11 was measured in the presence of the cations Ca2+, Mn2+, Zn2+, Co2+, Cu2+, Mg2+, and Fe3+ with EGTA as a negative control, and relative fluorescence measured against time (min). FIG
78 82 Ca2+ chemical The cleavage of Bz-R-AMC by PmC11 was measured in the presence of the cations Ca2+, Mn2+, Zn2+, Co2+, Cu2+, Mg2+, and Fe3+ with EGTA as a negative control, and relative fluorescence measured against time (min). FIG
84 88 Mn2+ chemical The cleavage of Bz-R-AMC by PmC11 was measured in the presence of the cations Ca2+, Mn2+, Zn2+, Co2+, Cu2+, Mg2+, and Fe3+ with EGTA as a negative control, and relative fluorescence measured against time (min). FIG
90 94 Zn2+ chemical The cleavage of Bz-R-AMC by PmC11 was measured in the presence of the cations Ca2+, Mn2+, Zn2+, Co2+, Cu2+, Mg2+, and Fe3+ with EGTA as a negative control, and relative fluorescence measured against time (min). FIG
96 100 Co2+ chemical The cleavage of Bz-R-AMC by PmC11 was measured in the presence of the cations Ca2+, Mn2+, Zn2+, Co2+, Cu2+, Mg2+, and Fe3+ with EGTA as a negative control, and relative fluorescence measured against time (min). FIG
102 106 Cu2+ chemical The cleavage of Bz-R-AMC by PmC11 was measured in the presence of the cations Ca2+, Mn2+, Zn2+, Co2+, Cu2+, Mg2+, and Fe3+ with EGTA as a negative control, and relative fluorescence measured against time (min). FIG
108 112 Mg2+ chemical The cleavage of Bz-R-AMC by PmC11 was measured in the presence of the cations Ca2+, Mn2+, Zn2+, Co2+, Cu2+, Mg2+, and Fe3+ with EGTA as a negative control, and relative fluorescence measured against time (min). FIG
118 122 Fe3+ chemical The cleavage of Bz-R-AMC by PmC11 was measured in the presence of the cations Ca2+, Mn2+, Zn2+, Co2+, Cu2+, Mg2+, and Fe3+ with EGTA as a negative control, and relative fluorescence measured against time (min). FIG
128 132 EGTA chemical The cleavage of Bz-R-AMC by PmC11 was measured in the presence of the cations Ca2+, Mn2+, Zn2+, Co2+, Cu2+, Mg2+, and Fe3+ with EGTA as a negative control, and relative fluorescence measured against time (min). FIG
160 203 relative fluorescence measured against time experimental_method The cleavage of Bz-R-AMC by PmC11 was measured in the presence of the cations Ca2+, Mn2+, Zn2+, Co2+, Cu2+, Mg2+, and Fe3+ with EGTA as a negative control, and relative fluorescence measured against time (min). FIG
4 23 addition of cations experimental_method The addition of cations produced no improvement in activity of PmC11 when compared in the presence of EGTA, suggesting that PmC11 does not require metal ions for proteolytic activity. FIG
63 68 PmC11 protein The addition of cations produced no improvement in activity of PmC11 when compared in the presence of EGTA, suggesting that PmC11 does not require metal ions for proteolytic activity. FIG
102 106 EGTA chemical The addition of cations produced no improvement in activity of PmC11 when compared in the presence of EGTA, suggesting that PmC11 does not require metal ions for proteolytic activity. FIG
124 129 PmC11 protein The addition of cations produced no improvement in activity of PmC11 when compared in the presence of EGTA, suggesting that PmC11 does not require metal ions for proteolytic activity. FIG
13 17 Cu2+ chemical Furthermore, Cu2+, Fe2+, and Zn2+ appear to inhibit PmC11. FIG
19 23 Fe2+ chemical Furthermore, Cu2+, Fe2+, and Zn2+ appear to inhibit PmC11. FIG
29 33 Zn2+ chemical Furthermore, Cu2+, Fe2+, and Zn2+ appear to inhibit PmC11. FIG
44 51 inhibit protein_state Furthermore, Cu2+, Fe2+, and Zn2+ appear to inhibit PmC11. FIG
52 57 PmC11 protein Furthermore, Cu2+, Fe2+, and Zn2+ appear to inhibit PmC11. FIG
16 27 Clostripain protein Comparison with Clostripain RESULTS
0 11 Clostripain protein Clostripain from C. histolyticum is the founding member of the C11 family of peptidases and contains an additional 149 residues compared with PmC11. RESULTS
17 32 C. histolyticum species Clostripain from C. histolyticum is the founding member of the C11 family of peptidases and contains an additional 149 residues compared with PmC11. RESULTS
63 73 C11 family protein_type Clostripain from C. histolyticum is the founding member of the C11 family of peptidases and contains an additional 149 residues compared with PmC11. RESULTS
77 87 peptidases protein_type Clostripain from C. histolyticum is the founding member of the C11 family of peptidases and contains an additional 149 residues compared with PmC11. RESULTS
115 127 149 residues residue_range Clostripain from C. histolyticum is the founding member of the C11 family of peptidases and contains an additional 149 residues compared with PmC11. RESULTS
142 147 PmC11 protein Clostripain from C. histolyticum is the founding member of the C11 family of peptidases and contains an additional 149 residues compared with PmC11. RESULTS
2 29 multiple sequence alignment experimental_method A multiple sequence alignment revealed that most of the secondary structural elements are conserved between the two enzymes, although they are only ∼23% identical (Fig. 1A). RESULTS
56 85 secondary structural elements structure_element A multiple sequence alignment revealed that most of the secondary structural elements are conserved between the two enzymes, although they are only ∼23% identical (Fig. 1A). RESULTS
90 99 conserved protein_state A multiple sequence alignment revealed that most of the secondary structural elements are conserved between the two enzymes, although they are only ∼23% identical (Fig. 1A). RESULTS
14 19 PmC11 protein Nevertheless, PmC11 may be a good model for the core structure of clostripain. RESULTS
66 77 clostripain protein Nevertheless, PmC11 may be a good model for the core structure of clostripain. RESULTS
4 32 primary structural alignment experimental_method The primary structural alignment also shows that the catalytic dyad in PmC11 is structurally conserved in clostripain (Fig. 1A). RESULTS
53 67 catalytic dyad site The primary structural alignment also shows that the catalytic dyad in PmC11 is structurally conserved in clostripain (Fig. 1A). RESULTS
71 76 PmC11 protein The primary structural alignment also shows that the catalytic dyad in PmC11 is structurally conserved in clostripain (Fig. 1A). RESULTS
80 102 structurally conserved protein_state The primary structural alignment also shows that the catalytic dyad in PmC11 is structurally conserved in clostripain (Fig. 1A). RESULTS
106 117 clostripain protein The primary structural alignment also shows that the catalytic dyad in PmC11 is structurally conserved in clostripain (Fig. 1A). RESULTS
7 12 PmC11 protein Unlike PmC11, clostripain has two cleavage sites (Arg181 and Arg190), which results in the removal of a nonapeptide, and is required for full activation of the enzyme (highlighted in Fig. 1A). RESULTS
14 25 clostripain protein Unlike PmC11, clostripain has two cleavage sites (Arg181 and Arg190), which results in the removal of a nonapeptide, and is required for full activation of the enzyme (highlighted in Fig. 1A). RESULTS
34 48 cleavage sites site Unlike PmC11, clostripain has two cleavage sites (Arg181 and Arg190), which results in the removal of a nonapeptide, and is required for full activation of the enzyme (highlighted in Fig. 1A). RESULTS
50 56 Arg181 residue_name_number Unlike PmC11, clostripain has two cleavage sites (Arg181 and Arg190), which results in the removal of a nonapeptide, and is required for full activation of the enzyme (highlighted in Fig. 1A). RESULTS
61 67 Arg190 residue_name_number Unlike PmC11, clostripain has two cleavage sites (Arg181 and Arg190), which results in the removal of a nonapeptide, and is required for full activation of the enzyme (highlighted in Fig. 1A). RESULTS
104 115 nonapeptide structure_element Unlike PmC11, clostripain has two cleavage sites (Arg181 and Arg190), which results in the removal of a nonapeptide, and is required for full activation of the enzyme (highlighted in Fig. 1A). RESULTS
137 152 full activation protein_state Unlike PmC11, clostripain has two cleavage sites (Arg181 and Arg190), which results in the removal of a nonapeptide, and is required for full activation of the enzyme (highlighted in Fig. 1A). RESULTS
15 21 Arg190 residue_name_number Interestingly, Arg190 was found to align with Lys147 in PmC11. RESULTS
46 52 Lys147 residue_name_number Interestingly, Arg190 was found to align with Lys147 in PmC11. RESULTS
56 61 PmC11 protein Interestingly, Arg190 was found to align with Lys147 in PmC11. RESULTS
35 53 S1-binding residue site In addition, the predicted primary S1-binding residue in PmC11 Asp177 also overlays with the residue predicted to be the P1 specificity determining residue in clostripain (Asp229, Fig. 1A). RESULTS
57 62 PmC11 protein In addition, the predicted primary S1-binding residue in PmC11 Asp177 also overlays with the residue predicted to be the P1 specificity determining residue in clostripain (Asp229, Fig. 1A). RESULTS
63 69 Asp177 residue_name_number In addition, the predicted primary S1-binding residue in PmC11 Asp177 also overlays with the residue predicted to be the P1 specificity determining residue in clostripain (Asp229, Fig. 1A). RESULTS
75 83 overlays experimental_method In addition, the predicted primary S1-binding residue in PmC11 Asp177 also overlays with the residue predicted to be the P1 specificity determining residue in clostripain (Asp229, Fig. 1A). RESULTS
121 155 P1 specificity determining residue site In addition, the predicted primary S1-binding residue in PmC11 Asp177 also overlays with the residue predicted to be the P1 specificity determining residue in clostripain (Asp229, Fig. 1A). RESULTS
159 170 clostripain protein In addition, the predicted primary S1-binding residue in PmC11 Asp177 also overlays with the residue predicted to be the P1 specificity determining residue in clostripain (Asp229, Fig. 1A). RESULTS
172 178 Asp229 residue_name_number In addition, the predicted primary S1-binding residue in PmC11 Asp177 also overlays with the residue predicted to be the P1 specificity determining residue in clostripain (Asp229, Fig. 1A). RESULTS
14 25 clostripain protein As studies on clostripain revealed addition of Ca2+ ions are required for full activation, the Ca2+ dependence of PmC11 was examined. RESULTS
47 51 Ca2+ chemical As studies on clostripain revealed addition of Ca2+ ions are required for full activation, the Ca2+ dependence of PmC11 was examined. RESULTS
74 89 full activation protein_state As studies on clostripain revealed addition of Ca2+ ions are required for full activation, the Ca2+ dependence of PmC11 was examined. RESULTS
95 99 Ca2+ chemical As studies on clostripain revealed addition of Ca2+ ions are required for full activation, the Ca2+ dependence of PmC11 was examined. RESULTS
114 119 PmC11 protein As studies on clostripain revealed addition of Ca2+ ions are required for full activation, the Ca2+ dependence of PmC11 was examined. RESULTS
14 18 Ca2+ chemical Surprisingly, Ca2+ did not enhance PmC11 activity and, furthermore, other divalent cations, Mg2+, Mn2+, Co2+, Fe2+, Zn2+, and Cu2+, were not necessary for PmC11 activity (Fig. 3D). RESULTS
35 40 PmC11 protein Surprisingly, Ca2+ did not enhance PmC11 activity and, furthermore, other divalent cations, Mg2+, Mn2+, Co2+, Fe2+, Zn2+, and Cu2+, were not necessary for PmC11 activity (Fig. 3D). RESULTS
92 96 Mg2+ chemical Surprisingly, Ca2+ did not enhance PmC11 activity and, furthermore, other divalent cations, Mg2+, Mn2+, Co2+, Fe2+, Zn2+, and Cu2+, were not necessary for PmC11 activity (Fig. 3D). RESULTS
98 102 Mn2+ chemical Surprisingly, Ca2+ did not enhance PmC11 activity and, furthermore, other divalent cations, Mg2+, Mn2+, Co2+, Fe2+, Zn2+, and Cu2+, were not necessary for PmC11 activity (Fig. 3D). RESULTS
104 108 Co2+ chemical Surprisingly, Ca2+ did not enhance PmC11 activity and, furthermore, other divalent cations, Mg2+, Mn2+, Co2+, Fe2+, Zn2+, and Cu2+, were not necessary for PmC11 activity (Fig. 3D). RESULTS
110 114 Fe2+ chemical Surprisingly, Ca2+ did not enhance PmC11 activity and, furthermore, other divalent cations, Mg2+, Mn2+, Co2+, Fe2+, Zn2+, and Cu2+, were not necessary for PmC11 activity (Fig. 3D). RESULTS
116 120 Zn2+ chemical Surprisingly, Ca2+ did not enhance PmC11 activity and, furthermore, other divalent cations, Mg2+, Mn2+, Co2+, Fe2+, Zn2+, and Cu2+, were not necessary for PmC11 activity (Fig. 3D). RESULTS
126 130 Cu2+ chemical Surprisingly, Ca2+ did not enhance PmC11 activity and, furthermore, other divalent cations, Mg2+, Mn2+, Co2+, Fe2+, Zn2+, and Cu2+, were not necessary for PmC11 activity (Fig. 3D). RESULTS
155 160 PmC11 protein Surprisingly, Ca2+ did not enhance PmC11 activity and, furthermore, other divalent cations, Mg2+, Mn2+, Co2+, Fe2+, Zn2+, and Cu2+, were not necessary for PmC11 activity (Fig. 3D). RESULTS
30 34 EGTA chemical In support of these findings, EGTA did not inhibit PmC11 suggesting that, unlike clostripain, PmC11 does not require Ca2+ or other divalent cations, for activity. RESULTS
51 56 PmC11 protein In support of these findings, EGTA did not inhibit PmC11 suggesting that, unlike clostripain, PmC11 does not require Ca2+ or other divalent cations, for activity. RESULTS
81 92 clostripain protein In support of these findings, EGTA did not inhibit PmC11 suggesting that, unlike clostripain, PmC11 does not require Ca2+ or other divalent cations, for activity. RESULTS
94 99 PmC11 protein In support of these findings, EGTA did not inhibit PmC11 suggesting that, unlike clostripain, PmC11 does not require Ca2+ or other divalent cations, for activity. RESULTS
117 121 Ca2+ chemical In support of these findings, EGTA did not inhibit PmC11 suggesting that, unlike clostripain, PmC11 does not require Ca2+ or other divalent cations, for activity. RESULTS
4 21 crystal structure evidence The crystal structure of PmC11 now provides three-dimensional information for a member of the clostripain C11 family of cysteine peptidases. DISCUSS
25 30 PmC11 protein The crystal structure of PmC11 now provides three-dimensional information for a member of the clostripain C11 family of cysteine peptidases. DISCUSS
94 105 clostripain protein The crystal structure of PmC11 now provides three-dimensional information for a member of the clostripain C11 family of cysteine peptidases. DISCUSS
106 116 C11 family protein_type The crystal structure of PmC11 now provides three-dimensional information for a member of the clostripain C11 family of cysteine peptidases. DISCUSS
120 139 cysteine peptidases protein_type The crystal structure of PmC11 now provides three-dimensional information for a member of the clostripain C11 family of cysteine peptidases. DISCUSS
58 73 clan CD members protein_type The enzyme exhibits all of the key structural elements of clan CD members, but is unusual in that it has a nine-stranded central β-sheet with a novel C-terminal domain. DISCUSS
129 136 β-sheet structure_element The enzyme exhibits all of the key structural elements of clan CD members, but is unusual in that it has a nine-stranded central β-sheet with a novel C-terminal domain. DISCUSS
150 167 C-terminal domain structure_element The enzyme exhibits all of the key structural elements of clan CD members, but is unusual in that it has a nine-stranded central β-sheet with a novel C-terminal domain. DISCUSS
29 34 PmC11 protein The structural similarity of PmC11 with its nearest structural neighbors in the PDB is decidedly low, overlaying better with six-stranded caspase-7 than any of the other larger members of the clan (Table 2). DISCUSS
138 147 caspase-7 protein The structural similarity of PmC11 with its nearest structural neighbors in the PDB is decidedly low, overlaying better with six-stranded caspase-7 than any of the other larger members of the clan (Table 2). DISCUSS
29 34 PmC11 protein The substrate specificity of PmC11 is Arg/Lys and the crystal structure revealed an acidic pocket for specific binding of such basic substrates. DISCUSS
38 41 Arg residue_name The substrate specificity of PmC11 is Arg/Lys and the crystal structure revealed an acidic pocket for specific binding of such basic substrates. DISCUSS
42 45 Lys residue_name The substrate specificity of PmC11 is Arg/Lys and the crystal structure revealed an acidic pocket for specific binding of such basic substrates. DISCUSS
54 71 crystal structure evidence The substrate specificity of PmC11 is Arg/Lys and the crystal structure revealed an acidic pocket for specific binding of such basic substrates. DISCUSS
84 97 acidic pocket site The substrate specificity of PmC11 is Arg/Lys and the crystal structure revealed an acidic pocket for specific binding of such basic substrates. DISCUSS
17 26 structure evidence In addition, the structure suggested a mechanism of self-inhibition in both PmC11 and clostripain and an activation mechanism that requires autoprocessing. DISCUSS
76 81 PmC11 protein In addition, the structure suggested a mechanism of self-inhibition in both PmC11 and clostripain and an activation mechanism that requires autoprocessing. DISCUSS
86 97 clostripain protein In addition, the structure suggested a mechanism of self-inhibition in both PmC11 and clostripain and an activation mechanism that requires autoprocessing. DISCUSS
140 154 autoprocessing ptm In addition, the structure suggested a mechanism of self-inhibition in both PmC11 and clostripain and an activation mechanism that requires autoprocessing. DISCUSS
0 5 PmC11 protein PmC11 differs from clostripain in that is does not appear to require divalent cations for activation. DISCUSS
19 30 clostripain protein PmC11 differs from clostripain in that is does not appear to require divalent cations for activation. DISCUSS
25 32 clan CD protein_type Several other members of clan CD require processing for full activation including legumain, gingipain-R, MARTX-CPD, and the effector caspases, e.g. caspase-7. DISCUSS
41 51 processing ptm Several other members of clan CD require processing for full activation including legumain, gingipain-R, MARTX-CPD, and the effector caspases, e.g. caspase-7. DISCUSS
56 71 full activation protein_state Several other members of clan CD require processing for full activation including legumain, gingipain-R, MARTX-CPD, and the effector caspases, e.g. caspase-7. DISCUSS
82 90 legumain protein Several other members of clan CD require processing for full activation including legumain, gingipain-R, MARTX-CPD, and the effector caspases, e.g. caspase-7. DISCUSS
92 103 gingipain-R protein Several other members of clan CD require processing for full activation including legumain, gingipain-R, MARTX-CPD, and the effector caspases, e.g. caspase-7. DISCUSS
105 114 MARTX-CPD protein Several other members of clan CD require processing for full activation including legumain, gingipain-R, MARTX-CPD, and the effector caspases, e.g. caspase-7. DISCUSS
124 141 effector caspases protein_type Several other members of clan CD require processing for full activation including legumain, gingipain-R, MARTX-CPD, and the effector caspases, e.g. caspase-7. DISCUSS
148 157 caspase-7 protein Several other members of clan CD require processing for full activation including legumain, gingipain-R, MARTX-CPD, and the effector caspases, e.g. caspase-7. DISCUSS
13 30 effector caspases protein_type To date, the effector caspases are the only group of enzymes that require cleavage of a loop within the central β-sheet. DISCUSS
74 82 cleavage ptm To date, the effector caspases are the only group of enzymes that require cleavage of a loop within the central β-sheet. DISCUSS
88 92 loop structure_element To date, the effector caspases are the only group of enzymes that require cleavage of a loop within the central β-sheet. DISCUSS
112 119 β-sheet structure_element To date, the effector caspases are the only group of enzymes that require cleavage of a loop within the central β-sheet. DISCUSS
25 30 PmC11 protein This is also the case in PmC11, although the cleavage loop is structurally different to that found in the caspases and follows the catalytic His (Fig. 1A), as opposed to the Cys in the caspases. DISCUSS
45 53 cleavage ptm This is also the case in PmC11, although the cleavage loop is structurally different to that found in the caspases and follows the catalytic His (Fig. 1A), as opposed to the Cys in the caspases. DISCUSS
54 58 loop structure_element This is also the case in PmC11, although the cleavage loop is structurally different to that found in the caspases and follows the catalytic His (Fig. 1A), as opposed to the Cys in the caspases. DISCUSS
106 114 caspases protein_type This is also the case in PmC11, although the cleavage loop is structurally different to that found in the caspases and follows the catalytic His (Fig. 1A), as opposed to the Cys in the caspases. DISCUSS
131 140 catalytic protein_state This is also the case in PmC11, although the cleavage loop is structurally different to that found in the caspases and follows the catalytic His (Fig. 1A), as opposed to the Cys in the caspases. DISCUSS
141 144 His residue_name This is also the case in PmC11, although the cleavage loop is structurally different to that found in the caspases and follows the catalytic His (Fig. 1A), as opposed to the Cys in the caspases. DISCUSS
174 177 Cys residue_name This is also the case in PmC11, although the cleavage loop is structurally different to that found in the caspases and follows the catalytic His (Fig. 1A), as opposed to the Cys in the caspases. DISCUSS
185 193 caspases protein_type This is also the case in PmC11, although the cleavage loop is structurally different to that found in the caspases and follows the catalytic His (Fig. 1A), as opposed to the Cys in the caspases. DISCUSS
10 25 clan CD members protein_type All other clan CD members requiring cleavage for full activation do so at sites external to their central sheets. DISCUSS
36 44 cleavage ptm All other clan CD members requiring cleavage for full activation do so at sites external to their central sheets. DISCUSS
49 64 full activation protein_state All other clan CD members requiring cleavage for full activation do so at sites external to their central sheets. DISCUSS
74 79 sites site All other clan CD members requiring cleavage for full activation do so at sites external to their central sheets. DISCUSS
106 112 sheets structure_element All other clan CD members requiring cleavage for full activation do so at sites external to their central sheets. DISCUSS
4 12 caspases protein_type The caspases and gingipain-R both undergo intermolecular (trans) cleavage and legumain and MARTX-CPD are reported to perform intramolecular (cis) cleavage. DISCUSS
17 28 gingipain-R protein The caspases and gingipain-R both undergo intermolecular (trans) cleavage and legumain and MARTX-CPD are reported to perform intramolecular (cis) cleavage. DISCUSS
42 73 intermolecular (trans) cleavage ptm The caspases and gingipain-R both undergo intermolecular (trans) cleavage and legumain and MARTX-CPD are reported to perform intramolecular (cis) cleavage. DISCUSS
78 86 legumain protein The caspases and gingipain-R both undergo intermolecular (trans) cleavage and legumain and MARTX-CPD are reported to perform intramolecular (cis) cleavage. DISCUSS
91 100 MARTX-CPD protein The caspases and gingipain-R both undergo intermolecular (trans) cleavage and legumain and MARTX-CPD are reported to perform intramolecular (cis) cleavage. DISCUSS
125 154 intramolecular (cis) cleavage ptm The caspases and gingipain-R both undergo intermolecular (trans) cleavage and legumain and MARTX-CPD are reported to perform intramolecular (cis) cleavage. DISCUSS
32 39 clan CD protein_type In addition, several members of clan CD exhibit self-inhibition, whereby regions of the enzyme block access to the active site. DISCUSS
73 80 regions structure_element In addition, several members of clan CD exhibit self-inhibition, whereby regions of the enzyme block access to the active site. DISCUSS
115 126 active site site In addition, several members of clan CD exhibit self-inhibition, whereby regions of the enzyme block access to the active site. DISCUSS
5 10 PmC11 protein Like PmC11, these structures show preformed catalytic machinery and, for a substrate to gain access, movement and/or cleavage of the blocking region is required. DISCUSS
117 125 cleavage ptm Like PmC11, these structures show preformed catalytic machinery and, for a substrate to gain access, movement and/or cleavage of the blocking region is required. DISCUSS
133 148 blocking region structure_element Like PmC11, these structures show preformed catalytic machinery and, for a substrate to gain access, movement and/or cleavage of the blocking region is required. DISCUSS
4 13 structure evidence The structure of PmC11 gives the first insight into this class of relatively unexplored family of proteins and should allow important catalytic and substrate binding residues to be identified in a variety of orthologues. DISCUSS
17 22 PmC11 protein The structure of PmC11 gives the first insight into this class of relatively unexplored family of proteins and should allow important catalytic and substrate binding residues to be identified in a variety of orthologues. DISCUSS
48 53 PmC11 protein Indeed, insights gained from an analysis of the PmC11 structure revealed the identity of the Trypanosoma brucei PNT1 protein as a C11 cysteine peptidase with an essential role in organelle replication. DISCUSS
54 63 structure evidence Indeed, insights gained from an analysis of the PmC11 structure revealed the identity of the Trypanosoma brucei PNT1 protein as a C11 cysteine peptidase with an essential role in organelle replication. DISCUSS
93 111 Trypanosoma brucei species Indeed, insights gained from an analysis of the PmC11 structure revealed the identity of the Trypanosoma brucei PNT1 protein as a C11 cysteine peptidase with an essential role in organelle replication. DISCUSS
112 116 PNT1 protein Indeed, insights gained from an analysis of the PmC11 structure revealed the identity of the Trypanosoma brucei PNT1 protein as a C11 cysteine peptidase with an essential role in organelle replication. DISCUSS
130 152 C11 cysteine peptidase protein_type Indeed, insights gained from an analysis of the PmC11 structure revealed the identity of the Trypanosoma brucei PNT1 protein as a C11 cysteine peptidase with an essential role in organelle replication. DISCUSS
4 9 PmC11 protein The PmC11 structure should provide a good basis for structural modeling and, given the importance of other clan CD enzymes, this work should also advance the exploration of these peptidases and potentially identify new biologically important substrates. DISCUSS
10 19 structure evidence The PmC11 structure should provide a good basis for structural modeling and, given the importance of other clan CD enzymes, this work should also advance the exploration of these peptidases and potentially identify new biologically important substrates. DISCUSS
52 71 structural modeling experimental_method The PmC11 structure should provide a good basis for structural modeling and, given the importance of other clan CD enzymes, this work should also advance the exploration of these peptidases and potentially identify new biologically important substrates. DISCUSS
107 122 clan CD enzymes protein_type The PmC11 structure should provide a good basis for structural modeling and, given the importance of other clan CD enzymes, this work should also advance the exploration of these peptidases and potentially identify new biologically important substrates. DISCUSS
179 189 peptidases protein_type The PmC11 structure should provide a good basis for structural modeling and, given the importance of other clan CD enzymes, this work should also advance the exploration of these peptidases and potentially identify new biologically important substrates. DISCUSS
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