2c2z: Difference between revisions
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|PDB= 2c2z |SIZE=350|CAPTION= <scene name='initialview01'>2c2z</scene>, resolution 1.95Å | |PDB= 2c2z |SIZE=350|CAPTION= <scene name='initialview01'>2c2z</scene>, resolution 1.95Å | ||
|SITE= <scene name='pdbsite=AC1:Dtd+Binding+Site+For+Chain+B'>AC1</scene> | |SITE= <scene name='pdbsite=AC1:Dtd+Binding+Site+For+Chain+B'>AC1</scene> | ||
|LIGAND= <scene name='pdbligand=DTD:DITHIANE DIOL'>DTD</scene> | |LIGAND= <scene name='pdbligand=DTD:DITHIANE+DIOL'>DTD</scene>, <scene name='pdbligand=MX5:{1-[4-(3,4-DIHYDROQUINOLIN-1(2H)-YL)-4-OXOBUTANOYL]HYDRAZINO}ACETIC+ACID'>MX5</scene>, <scene name='pdbligand=PHQ:FORMIC+ACID+BENZYL+ESTER'>PHQ</scene> | ||
|ACTIVITY= | |ACTIVITY= | ||
|GENE= | |GENE= | ||
|DOMAIN= | |||
|RELATEDENTRY= | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2c2z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2c2z OCA], [http://www.ebi.ac.uk/pdbsum/2c2z PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2c2z RCSB]</span> | |||
}} | }} | ||
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==Overview== | ==Overview== | ||
Aza-peptide Michael acceptors are a novel class of inhibitors that are potent and specific for caspases-2, -3, -6, -7, -8, -9, and -10. The second-order rate constants are in the order of 10(6) M(-1) s(-1). The aza-peptide Michael acceptor inhibitor 18t (Cbz-Asp-Glu-Val-AAsp-trans-CH=CH-CON(CH(2)-1-Naphth)(2) is the most potent compound and it inhibits caspase-3 with a k(2) value of 5620000 M(-1) s(-1). The inhibitor 18t is 13700, 190, 6.4, 594, 37500, and 173-fold more selective for caspase-3 over caspases-2, -6, -7, -8, -9, and -10, respectively. Aza-peptide Michael acceptors designed with caspase specific sequences are selective and do not show any cross reactivity with clan CA cysteine proteases such as papain, cathepsin B, and calpains. High-resolution crystal structures of caspase-3 and caspase-8 in complex with aza-peptide Michael acceptor inhibitors demonstrate the nucleophilic attack on C2 and provide insight into the selectivity and potency of the inhibitors with respect to the P1' moiety. | Aza-peptide Michael acceptors are a novel class of inhibitors that are potent and specific for caspases-2, -3, -6, -7, -8, -9, and -10. The second-order rate constants are in the order of 10(6) M(-1) s(-1). The aza-peptide Michael acceptor inhibitor 18t (Cbz-Asp-Glu-Val-AAsp-trans-CH=CH-CON(CH(2)-1-Naphth)(2) is the most potent compound and it inhibits caspase-3 with a k(2) value of 5620000 M(-1) s(-1). The inhibitor 18t is 13700, 190, 6.4, 594, 37500, and 173-fold more selective for caspase-3 over caspases-2, -6, -7, -8, -9, and -10, respectively. Aza-peptide Michael acceptors designed with caspase specific sequences are selective and do not show any cross reactivity with clan CA cysteine proteases such as papain, cathepsin B, and calpains. High-resolution crystal structures of caspase-3 and caspase-8 in complex with aza-peptide Michael acceptor inhibitors demonstrate the nucleophilic attack on C2 and provide insight into the selectivity and potency of the inhibitors with respect to the P1' moiety. | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Powers, J C.]] | [[Category: Powers, J C.]] | ||
[[Category: Salvesen, G S.]] | [[Category: Salvesen, G S.]] | ||
[[Category: apoptosis]] | [[Category: apoptosis]] | ||
[[Category: aza-asp]] | [[Category: aza-asp]] | ||
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[[Category: zymogen]] | [[Category: zymogen]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 02:15:32 2008'' | ||
