2cjy: Difference between revisions

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New page: left|200px<br /> <applet load="2cjy" size="450" color="white" frame="true" align="right" spinBox="true" caption="2cjy, resolution 1.67Å" /> '''EXTENDED SUBSTRATE ...
 
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[[Image:2cjy.gif|left|200px]]<br />
<applet load="2cjy" size="450" color="white" frame="true" align="right" spinBox="true"
caption="2cjy, resolution 1.67&Aring;" />
'''EXTENDED SUBSTRATE RECOGNITION IN CASPASE-3 REVEALED BY HIGH RESOLUTION X-RAY STRUCTURE ANALYSIS'''<br />


==Overview==
==Extended substrate recognition in caspase-3 revealed by high resolution X-ray structure analysis==
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 ... [[http://ispc.weizmann.ac.il/pmbin/getpm?16787777 (full description)]]
<StructureSection load='2cjy' size='340' side='right'caption='[[2cjy]], [[Resolution|resolution]] 1.67&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2cjy]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2CJY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2CJY FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.67&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0QE:CHLOROMETHANE'>0QE</scene>, <scene name='pdbligand=PHQ:BENZYL+CHLOROCARBONATE'>PHQ</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2cjy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2cjy OCA], [https://pdbe.org/2cjy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2cjy RCSB], [https://www.ebi.ac.uk/pdbsum/2cjy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2cjy ProSAT]</span></td></tr>
</table>
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/cj/2cjy_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2cjy ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
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==
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<ref>PMID:16787777</ref>
2CJY is a [[http://en.wikipedia.org/wiki/Protein_complex Protein complex]] structure of sequences from [[http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]] with PHQ as [[http://en.wikipedia.org/wiki/ligand ligand]]. Full crystallographic information is available from [[http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2CJY OCA]].


==Reference==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16787777 16787777]
</div>
<div class="pdbe-citations 2cjy" style="background-color:#fffaf0;"></div>
 
==See Also==
*[[Caspase 3D structures|Caspase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Protein complex]]
[[Category: Large Structures]]
[[Category: Ganesan, R.]]
[[Category: Synthetic construct]]
[[Category: Grutter, M.G.]]
[[Category: Ganesan R]]
[[Category: Jelakovic, S.]]
[[Category: Grutter MG]]
[[Category: Mittl, P.R.E.]]
[[Category: Jelakovic S]]
[[Category: PHQ]]
[[Category: Mittl PRE]]
[[Category: apoptosis]]
[[Category: clan cd]]
[[Category: complex (hydrolase-inhibitor)]]
[[Category: complex (protease-inhibitor)]]
[[Category: cpp32]]
[[Category: cysteine-protease]]
[[Category: hydrolase]]
[[Category: ice]]
[[Category: phosphorylation]]
[[Category: polymorphism]]
[[Category: protease]]
[[Category: safety catch]]
[[Category: tetramer]]
[[Category: thiol protease]]
[[Category: yama]]
[[Category: zymogen]]
 
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Oct 29 21:00:21 2007''

Latest revision as of 00:50, 21 November 2024

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

2cjy, resolution 1.67Å

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