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[[Image:1gqf.gif|left|200px]]
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{{STRUCTURE_1gqf|  PDB=1gqf  |  SCENE=  }}
'''CRYSTAL STRUCTURE OF HUMAN PROCASPASE-7'''


==Crystal structure of human procaspase-7==
<StructureSection load='1gqf' size='340' side='right'caption='[[1gqf]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1gqf]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1GQF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1GQF 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]] 2.9&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=1gqf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1gqf OCA], [https://pdbe.org/1gqf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1gqf RCSB], [https://www.ebi.ac.uk/pdbsum/1gqf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1gqf ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/CASP7_HUMAN CASP7_HUMAN] Involved in the activation cascade of caspases responsible for apoptosis execution. Cleaves and activates sterol regulatory element binding proteins (SREBPs). Proteolytically cleaves poly(ADP-ribose) polymerase (PARP) at a '216-Asp-|-Gly-217' bond. Overexpression promotes programmed cell death.
== 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/gq/1gqf_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.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=1gqf ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Caspases form a family of proteinases required for the initiation and execution phases of apoptosis. Distinct proapoptotic stimuli lead to activation of the initiator caspases-8 and -9, which in turn activate the common executioner caspases-3 and -7 by proteolytic cleavage. Whereas crystal structures of several active caspases have been reported, no three-dimensional structure of an uncleaved caspase zymogen is available so far. We have determined the 2.9-A crystal structure of recombinant human C285A procaspase-7 and have elucidated the activation mechanism of caspases. The overall fold of the homodimeric procaspase-7 resembles that of the active tetrameric caspase-7. Each monomer is organized in two structured subdomains connected by partially flexible linkers, which asymmetrically occupy and block the central cavity, a typical feature of active caspases. This blockage is incompatible with a functional substrate binding site/active site. After proteolytic cleavage within the flexible linkers, the newly formed chain termini leave the cavity and fold outward to form stable structures. These conformational changes are associated with the formation of an intact active-site cleft. Therefore, this mechanism represents a formerly unknown type of proteinase zymogen activation.


==Overview==
Structural basis for the activation of human procaspase-7.,Riedl SJ, Fuentes-Prior P, Renatus M, Kairies N, Krapp S, Huber R, Salvesen GS, Bode W Proc Natl Acad Sci U S A. 2001 Dec 18;98(26):14790-5. PMID:11752425<ref>PMID:11752425</ref>
Caspases form a family of proteinases required for the initiation and execution phases of apoptosis. Distinct proapoptotic stimuli lead to activation of the initiator caspases-8 and -9, which in turn activate the common executioner caspases-3 and -7 by proteolytic cleavage. Whereas crystal structures of several active caspases have been reported, no three-dimensional structure of an uncleaved caspase zymogen is available so far. We have determined the 2.9-A crystal structure of recombinant human C285A procaspase-7 and have elucidated the activation mechanism of caspases. The overall fold of the homodimeric procaspase-7 resembles that of the active tetrameric caspase-7. Each monomer is organized in two structured subdomains connected by partially flexible linkers, which asymmetrically occupy and block the central cavity, a typical feature of active caspases. This blockage is incompatible with a functional substrate binding site/active site. After proteolytic cleavage within the flexible linkers, the newly formed chain termini leave the cavity and fold outward to form stable structures. These conformational changes are associated with the formation of an intact active-site cleft. Therefore, this mechanism represents a formerly unknown type of proteinase zymogen activation.


==About this Structure==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
1GQF is a [[Single protein]] structure of sequence 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=1GQF OCA].
</div>
<div class="pdbe-citations 1gqf" style="background-color:#fffaf0;"></div>


==Reference==
==See Also==
Structural basis for the activation of human procaspase-7., Riedl SJ, Fuentes-Prior P, Renatus M, Kairies N, Krapp S, Huber R, Salvesen GS, Bode W, Proc Natl Acad Sci U S A. 2001 Dec 18;98(26):14790-5. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/11752425 11752425]
*[[Caspase 3D structures|Caspase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Bode, W.]]
[[Category: Bode W]]
[[Category: Fuentes-Prior, P.]]
[[Category: Fuentes-Prior P]]
[[Category: Riedl, S.]]
[[Category: Riedl S]]
[[Category: Apoptosis]]
[[Category: Caspase-7]]
[[Category: Hydrolase]]
[[Category: Zymogen]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May  2 17:53:29 2008''