2dko: Difference between revisions

Revision as of 17:59, 21 February 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 Thu Feb 21 16:59:44 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]]<br />
+[[Image:2dko.gif|left|200px]]<br /><applet load="2dko" size="350" color="white" frame="true" align="right" spinBox="true"
-<applet load="2dko" size="450" color="white" frame="true" align="right" spinBox="true"
 caption="2dko, resolution 1.06&Aring;" />
 '''Extended substrate recognition in caspase-3 revealed by high resolution X-ray structure analysis'''<br />
 ==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.
+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==
-DKO is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2DKO OCA].
+DKO is a [http://en.wikipedia.org/wiki/Protein_complex 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=2DKO OCA].
 ==Reference==
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 [[Category: Protein complex]]
 [[Category: Ganesan, R.]]
-[[Category: Grutter, M.G.]]
+[[Category: Grutter, M G.]]
 [[Category: Jelakovic, S.]]
-[[Category: Mittl, P.R.E.]]
+[[Category: Mittl, P R.E.]]
 [[Category: caspase]]
 [[Category: drug design]]
@@ Line 25: / Line 24: @@
 [[Category: tetrahedral intermediate]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 21:34:58 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:59:44 2008''