2dko: Difference between revisions

Revision as of 00:37, 4 May 2008

Extended substrate recognition in caspase-3 revealed by high resolution X-ray structure analysis

OverviewOverview

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 StructureAbout this Structure

2DKO is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

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

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

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 [[Image:2dko.gif|left|200px]]
- {{Structure
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+The line below this paragraph, containing "STRUCTURE_2dko", creates the "Structure Box" on the page.
-|SITE=
+You may change the PDB parameter (which sets the PDB file loaded into the applet)
-|LIGAND= <scene name='pdbligand=AKL:3-AMINO-5-CHLORO-4-OXOPENTANOIC+ACID'>AKL</scene>
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-|RELATEDENTRY=
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2dko FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2dko OCA], [http://www.ebi.ac.uk/pdbsum/2dko PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2dko RCSB]</span>
-}}
 '''Extended substrate recognition in caspase-3 revealed by high resolution X-ray structure analysis'''
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 [[Category: Jelakovic, S.]]
 [[Category: Mittl, P R.E.]]
-[[Category: caspase]]
+[[Category: Caspase]]
-[[Category: drug design]]
+[[Category: Drug design]]
-[[Category: low barrier hydrogen bond]]
+[[Category: Low barrier hydrogen bond]]
-[[Category: protease]]
+[[Category: Protease]]
-[[Category: radiation damage]]
+[[Category: Radiation damage]]
-[[Category: tetrahedral intermediate]]
+[[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 Mon Mar 31 02:35:53 2008''