User:Christopher French: Difference between revisions

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Caspase 8 is a 58 kilodalton protein that shares similarities with other members of the caspase family. The protein is composed of two subunits, referred to as <scene name='User:Christopher_French/Subunits/1'>p18 and p11</scene>

Caspase 8 is a 58 kilodalton protein that shares similarities with other members of the caspase family. The protein is composed of two subunits, referred to as <scene name='User:Christopher_French/Subunits/1'>p18 and p11</scene>. These two subunits form a heterodimer. The protein has a α/ß folding motif that has a central six stranded beta sheet. Five of the strands are parallel and one is anti-parallel. The antiparallel strand is on the edge of the ß sheet. There are also six alpha helices in the protein structure. Three of these alpha helices are located on one side of the ß sheet and the other two on the other side, forming a <scene name='User:Christopher_French/Secondary_structure/3'>three layer sandwich</scene>. The p18 subunit has a Rossmann fold. There is a <scene

. These two subunits form a heterodimer. The protein has a α/ß folding motif that has a central six stranded beta sheet. Five of the strands are parallel and one is anti-parallel. The antiparallel strand is on the edge of the ß sheet. There are also six alpha helices in the protein structure. Three of these alpha helices are located on one side of the ß sheet and the other two on the other side, forming a <scene name='User:Christopher_French/Secondary_structure/3'>three layer sandwich</scene>. The p18 subunit has a Rossmann fold. There is a <scene

<scene name='User:Christopher_French/Turn_of_helix/2'>turn of helix</scene>

(α1’) which is part of a large loop (loop 1). This is along the binding pocket region of the p18 subunit. There is a two-stranded antiparallel ß sheet found at the top of the main ß sheet which forms the base of the binding pocket (4,5).

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'''Heterotetramer'''

Two p18-p11 heterodimers form a tetramer. This extends the six strands of the ß sheet to 12 strands. In the heterotetramer, the first segment of the P11 subunit and the last segment of the p18 subunit extend from the structure in an anti-parallel fashion and interact with the other heterodimer. <scene name='User:Christopher_French/Heterotetramer/1'>Residues 363-374 and 385-396</scene>of one heterodimer extend into the other heterodimer and interact with residues Thr390 and Asp395(4).

Two p18-p11 heterodimers form a tetramer. This extends the six strands of the ß sheet to 12 strands. In the heterotetramer, the first segment of the P11 subunit and the last segment of the p18 subunit extend from the structure in an anti-parallel fashion and interact with the other heterodimer. <scene name='User:Christopher_French/Heterotetramer/1'> Residues 363-374 and 385-396</scene>of one heterodimer extend into the other heterodimer and interact with residues Thr390 and Asp395(4).

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'''The active site'''

The catalytic triad in caspase 8 comprises <scene name='User:Christopher_French/Catalytic_triad/6'>Cys360, His317, and Arg258</scene>.<scene name='User:Christopher_French/Active_site_s1-s4/2'> See S1-S4 pockets.</scene

The catalytic triad in caspase 8 comprises <scene name='User:Christopher_French/Catalytic_triad/6'>Cys360, His317, and Arg258</scene>.<scene name='User:Christopher_French/Active_site_s1-s4/2'> See S1-S4 pockets.</scene>

. The carboxyl group of P1 aspartate forms a salt bridge with Arg413 and Arg260. It also forms hydrogen bonds to Gln358. The P1 α-carbonyl group rotates and the oxygen atom rehybridizes to become a hydroxyl group. This then forms a hydrogen bond with the imidazole group of His317. A clear interaction exists between the carbonyl oxygen of Arg258 and the Nє of His317. The S2 pocket Cγ atom of the threonine sidechain of P2 lies in a hydrophobic pocket that is formed from the sidechains of Val410 and Tyr412. The Oγ is surrounded by water molecules. The S3 pocket consists of a glutamate at P3 that sits in a cleft made by Arg413, Arg258, and Pro415, and Asn261. Arg413 forms a salt bridge to P3 glutamate and P1 aspartate sidechains. Arg413 also forms hydrogen bonds between its main chain atoms and the mainchain if the peptide inhibitor. The S4 pocket is especially important in selectivity. The acetyl of the inhibitor hydrogen bonds to the carboxyl group of P3 glutamate through a hydrogen bond. The hydrogen bond participants then move away to accommodate a non-polar residue. The faces of two aromatic residues, Trp420 and Tyr412 help form part of the hydrophobic S4 pocket (4).

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-Caspase 8 is a 58 kilodalton protein that shares similarities with other members of the caspase family. The protein is composed of two subunits, referred to as <scene name='User:Christopher_French/Subunits/1'>p18 and p11</scene>
+Caspase 8 is a 58 kilodalton protein that shares similarities with other members of the caspase family. The protein is composed of two subunits, referred to as <scene name='User:Christopher_French/Subunits/1'>p18 and p11</scene>. These two subunits form a heterodimer. The protein has a α/ß folding motif that has a central six stranded beta sheet. Five of the strands are parallel and one is anti-parallel. The antiparallel strand is on the edge of the ß sheet. There are also six alpha helices in the protein structure. Three of these alpha helices are located on one side of the ß sheet and the other two on the other side, forming a <scene name='User:Christopher_French/Secondary_structure/3'>three layer sandwich</scene>. The p18 subunit has a Rossmann fold. There is a <scene
-. These two subunits form a heterodimer. The protein has a α/ß folding motif that has a central six stranded beta sheet. Five of the strands are parallel and one is anti-parallel. The antiparallel strand is on the edge of the ß sheet. There are also six alpha helices in the protein structure. Three of these alpha helices are located on one side of the ß sheet and the other two on the other side, forming a <scene name='User:Christopher_French/Secondary_structure/3'>three layer sandwich</scene>. The p18 subunit has a Rossmann fold. There is a <scene
 <scene name='User:Christopher_French/Turn_of_helix/2'>turn of helix</scene>
   (α1’) which is part of a large loop (loop 1). This is along the binding pocket region of the p18 subunit. There is a two-stranded antiparallel ß sheet found at the top of the main ß sheet which forms the base of the binding pocket (4,5).
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 '''Heterotetramer'''
-Two p18-p11 heterodimers form a tetramer. This extends the six strands of the ß sheet to 12 strands. In the heterotetramer, the first segment of the P11 subunit and the last segment of the p18 subunit extend from the structure in an anti-parallel fashion and interact with the other heterodimer. <scene name='User:Christopher_French/Heterotetramer/1'>Residues 363-374 and 385-396</scene>of one heterodimer extend into the other heterodimer and interact with residues Thr390 and Asp395(4).
+Two p18-p11 heterodimers form a tetramer. This extends the six strands of the ß sheet to 12 strands. In the heterotetramer, the first segment of the P11 subunit and the last segment of the p18 subunit extend from the structure in an anti-parallel fashion and interact with the other heterodimer. <scene name='User:Christopher_French/Heterotetramer/1'> Residues 363-374 and 385-396</scene>of one heterodimer extend into the other heterodimer and interact with residues Thr390 and Asp395(4).
 ----
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 '''The active site'''
-The catalytic triad in caspase 8 comprises <scene name='User:Christopher_French/Catalytic_triad/6'>Cys360, His317, and Arg258</scene>.<scene name='User:Christopher_French/Active_site_s1-s4/2'> See S1-S4 pockets.</scene
+The catalytic triad in caspase 8 comprises <scene name='User:Christopher_French/Catalytic_triad/6'>Cys360, His317, and Arg258</scene>.<scene name='User:Christopher_French/Active_site_s1-s4/2'> See S1-S4 pockets.</scene>
 . The carboxyl group of P1 aspartate forms a salt bridge with Arg413 and Arg260. It also forms hydrogen bonds to Gln358. The P1 α-carbonyl group rotates and the oxygen atom rehybridizes to become a hydroxyl group. This then forms a hydrogen bond with the imidazole group of His317. A clear interaction exists between the carbonyl oxygen of Arg258 and the Nє of His317. The S2 pocket Cγ atom of the threonine sidechain of P2 lies in a hydrophobic pocket that is formed from the sidechains of Val410 and Tyr412. The Oγ is surrounded by water molecules. The S3 pocket consists of a glutamate at P3 that sits in a cleft made by Arg413, Arg258, and Pro415, and Asn261. Arg413 forms a salt bridge to P3 glutamate and P1 aspartate sidechains. Arg413 also forms hydrogen bonds between its main chain atoms and the mainchain if the peptide inhibitor. The S4 pocket is especially important in selectivity. The acetyl of the inhibitor hydrogen bonds to the carboxyl group of P3 glutamate through a hydrogen bond. The hydrogen bond participants then move away to accommodate a non-polar residue. The faces of two aromatic residues, Trp420 and Tyr412 help form part of the hydrophobic S4 pocket (4).