2c1e: Difference between revisions
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[[Image:2c1e.gif|left|200px]] | [[Image:2c1e.gif|left|200px]] | ||
'''CRYSTAL STRUCTURES OF CASPASE-3 IN COMPLEX WITH AZA-PEPTIDE MICHAEL ACCEPTOR INHIBITORS.''' | {{Structure | ||
|PDB= 2c1e |SIZE=350|CAPTION= <scene name='initialview01'>2c1e</scene>, resolution 1.77Å | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=PHQ:FORMIC+ACID+BENZYL+ESTER'>PHQ</scene> and <scene name='pdbligand=AA1:[1-(4-ETHOXY-4-OXOBUTANOYL)HYDRAZINO]ACETIC ACID'>AA1</scene> | |||
|ACTIVITY= | |||
|GENE= | |||
}} | |||
'''CRYSTAL STRUCTURES OF CASPASE-3 IN COMPLEX WITH AZA-PEPTIDE MICHAEL ACCEPTOR INHIBITORS.''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
2C1E is a [ | 2C1E is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2C1E OCA]. | ||
==Reference== | ==Reference== | ||
Design, synthesis, and evaluation of aza-peptide Michael acceptors as selective and potent inhibitors of caspases-2, -3, -6, -7, -8, -9, and -10., Ekici OD, Li ZZ, Campbell AJ, James KE, Asgian JL, Mikolajczyk J, Salvesen GS, Ganesan R, Jelakovic S, Grutter MG, Powers JC, J Med Chem. 2006 Sep 21;49(19):5728-49. PMID:[http:// | Design, synthesis, and evaluation of aza-peptide Michael acceptors as selective and potent inhibitors of caspases-2, -3, -6, -7, -8, -9, and -10., Ekici OD, Li ZZ, Campbell AJ, James KE, Asgian JL, Mikolajczyk J, Salvesen GS, Ganesan R, Jelakovic S, Grutter MG, Powers JC, J Med Chem. 2006 Sep 21;49(19):5728-49. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16970398 16970398] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
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[[Category: zymogen]] | [[Category: zymogen]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 16:09:30 2008'' | ||
Revision as of 17:09, 20 March 2008
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| , resolution 1.77Å | |||||||
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| Coordinates: | save as pdb, mmCIF, xml | ||||||
CRYSTAL STRUCTURES OF CASPASE-3 IN COMPLEX WITH AZA-PEPTIDE MICHAEL ACCEPTOR INHIBITORS.
OverviewOverview
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 StructureAbout this Structure
2C1E is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Design, synthesis, and evaluation of aza-peptide Michael acceptors as selective and potent inhibitors of caspases-2, -3, -6, -7, -8, -9, and -10., Ekici OD, Li ZZ, Campbell AJ, James KE, Asgian JL, Mikolajczyk J, Salvesen GS, Ganesan R, Jelakovic S, Grutter MG, Powers JC, J Med Chem. 2006 Sep 21;49(19):5728-49. PMID:16970398
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