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2cjx
From Proteopedia
(New page: 200px<br /> <applet load="2cjx" size="450" color="white" frame="true" align="right" spinBox="true" caption="2cjx, resolution 1.70Å" /> '''EXTENDED SUBSTRATE ...) |
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| - | [[Image:2cjx.gif|left|200px]]<br /> | + | [[Image:2cjx.gif|left|200px]]<br /><applet load="2cjx" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="2cjx" size=" | + | |
caption="2cjx, resolution 1.70Å" /> | caption="2cjx, resolution 1.70Å" /> | ||
'''EXTENDED SUBSTRATE RECOGNITION IN CASPASE-3 REVEALED BY HIGH RESOLUTION X-RAY STRUCTURE ANALYSIS'''<br /> | '''EXTENDED SUBSTRATE RECOGNITION IN CASPASE-3 REVEALED BY HIGH RESOLUTION X-RAY STRUCTURE ANALYSIS'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Caspases are cysteine proteases involved in the signalling cascades of | + | 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== | ==About this Structure== | ||
| - | 2CJX 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:// | + | 2CJX 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=2CJX OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Ganesan, R.]] | [[Category: Ganesan, R.]] | ||
| - | [[Category: Grutter, M | + | [[Category: Grutter, M G.]] |
[[Category: Jelakovic, S.]] | [[Category: Jelakovic, S.]] | ||
| - | [[Category: Mittl, P | + | [[Category: Mittl, P R.E.]] |
[[Category: apoptosis]] | [[Category: apoptosis]] | ||
[[Category: clan cd]] | [[Category: clan cd]] | ||
| Line 35: | Line 34: | ||
[[Category: zymogen]] | [[Category: zymogen]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:49:27 2008'' |
Revision as of 14:49, 21 February 2008
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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
2CJX 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 Thu Feb 21 16:49:27 2008
Categories: Homo sapiens | Protein complex | Ganesan, R. | Grutter, M G. | Jelakovic, S. | Mittl, P R.E. | Apoptosis | Clan cd | Complex (hydrolase-inhibitor) | Complex (protease-inhibitor) | Cpp32 | Cysteine-protease | Hydrolase | Ice | Phosphorylation | Polymorphism | Protease | Safety catch | Tetramer | Thiol protease | Yama | Zymogen
