2c1e: Difference between revisions

Revision as of 21:06, 3 May 2008

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 Page seeded by OCA on Sat May 3 21:05:59 2008

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OCA

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 [[Image:2c1e.gif|left|200px]]
- {{Structure
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+The line below this paragraph, containing "STRUCTURE_2c1e", creates the "Structure Box" on the page.
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-|LIGAND= <scene name='pdbligand=AA1:[1-(4-ETHOXY-4-OXOBUTANOYL)HYDRAZINO]ACETIC+ACID'>AA1</scene>, <scene name='pdbligand=PHQ:FORMIC+ACID+BENZYL+ESTER'>PHQ</scene>
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-|RELATEDENTRY=
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2c1e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2c1e OCA], [http://www.ebi.ac.uk/pdbsum/2c1e PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2c1e RCSB]</span>
-}}
 '''CRYSTAL STRUCTURES OF CASPASE-3 IN COMPLEX WITH AZA-PEPTIDE MICHAEL ACCEPTOR INHIBITORS.'''
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 [[Category: Protein complex]]
 [[Category: Grutter, M G.]]
-[[Category: apoptosis]]
+[[Category: Apoptosis]]
-[[Category: aza-peptide]]
+[[Category: Aza-peptide]]
-[[Category: clan cd]]
+[[Category: Clan cd]]
-[[Category: complex (protease-inhibitor)]]
+[[Category: Cpp32]]
-[[Category: cpp32]]
+[[Category: Cysteine-protease]]
-[[Category: cysteine-protease]]
+[[Category: Hydrolase]]
-[[Category: hydrolase]]
+[[Category: Michael acceptor,aza-asp]]
-[[Category: michael acceptor,aza-asp]]
+[[Category: Thiol protease,zymogen]]
-[[Category: thiol protease,zymogen]]
+[[Category: Yama]]
-[[Category: yama]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 21:05:59 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 02:14:53 2008''