2dko
From Proteopedia
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[[Image:2dko.gif|left|200px]] | [[Image:2dko.gif|left|200px]] | ||
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| - | + | {{STRUCTURE_2dko| PDB=2dko | SCENE= }} | |
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'''Extended substrate recognition in caspase-3 revealed by high resolution X-ray structure analysis''' | '''Extended substrate recognition in caspase-3 revealed by high resolution X-ray structure analysis''' | ||
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[[Category: Jelakovic, S.]] | [[Category: Jelakovic, S.]] | ||
[[Category: Mittl, P R.E.]] | [[Category: Mittl, P R.E.]] | ||
| - | [[Category: | + | [[Category: Caspase]] |
| - | [[Category: | + | [[Category: Drug design]] |
| - | [[Category: | + | [[Category: Low barrier hydrogen bond]] |
| - | [[Category: | + | [[Category: Protease]] |
| - | [[Category: | + | [[Category: Radiation damage]] |
| - | [[Category: | + | [[Category: Tetrahedral intermediate]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 00:37:26 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 21:37, 3 May 2008
Extended substrate recognition in caspase-3 revealed by high resolution X-ray structure analysis
Overview
Caspases are cysteine proteases involved in the signalling cascades of programmed cell death in which caspase-3 plays a central role, since it propagates death signals from intrinsic and extrinsic stimuli to downstream targets. The atomic resolution (1.06 Angstroms) crystal structure of the caspase-3 DEVD-cmk complex reveals the structural basis for substrate selectivity in the S4 pocket. A low-barrier hydrogen bond is observed between the side-chains of the P4 inhibitor aspartic acid and Asp179 of the N-terminal tail of the symmetry related p12 subunit. Site-directed mutagenesis of Asp179 confirmed the significance of this residue in substrate recognition. In the 1.06 Angstroms crystal structure, a radiation damage induced rearrangement of the inhibitor methylketone moiety was observed. The carbon atom that in a substrate would represent the scissile peptide bond carbonyl carbon clearly shows a tetrahedral coordination and resembles the postulated tetrahedral intermediate of the acylation reaction.
About this Structure
2DKO is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Extended substrate recognition in caspase-3 revealed by high resolution X-ray structure analysis., Ganesan R, Mittl PR, Jelakovic S, Grutter MG, J Mol Biol. 2006 Jun 23;359(5):1378-88. Epub 2006 May 11. PMID:16787777 Page seeded by OCA on Sun May 4 00:37:26 2008
