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[[Image: | ==Crystal structure of human CYP11A1 in complex with 20,22-dihydroxycholesterol== | ||
<StructureSection load='3na0' size='340' side='right' caption='[[3na0]], [[Resolution|resolution]] 2.50Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3na0]] is a 4 chain structure with 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=3NA0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3NA0 FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2DC:(3ALPHA,8ALPHA,22R)-CHOLEST-5-ENE-3,20,22-TRIOL'>2DC</scene>, <scene name='pdbligand=FES:FE2/S2+(INORGANIC)+CLUSTER'>FES</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3n9y|3n9y]], [[3n9z|3n9z]], [[3na1|3na1]]</td></tr> | |||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CYP11A, CYP11A1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), adrenodoxin, ADX, FDX1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr> | |||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Cholesterol_monooxygenase_(side-chain-cleaving) Cholesterol monooxygenase (side-chain-cleaving)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.15.6 1.14.15.6] </span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3na0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3na0 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3na0 RCSB], [http://www.ebi.ac.uk/pdbsum/3na0 PDBsum]</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/na/3na0_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/chain_selection.php?pdb_ID=2ata ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
In humans, the precursor to all steroid hormones, pregnenolone, is synthesized from cholesterol by an enzyme complex comprising adrenodoxin reductase (AdR), adrenodoxin (Adx), and a cytochrome P450 (P450scc or CYP11A1). This complex not only plays a key role in steroidogenesis, but also has long been a model to study electron transfer, multistep catalysis, and C-C bond cleavage performed by monooxygenases. Detailed mechanistic understanding of these processes has been hindered by a lack of structural information. Here we present the crystal structure of the complex of human Adx and CYP11A1-the first of a complex between a eukaryotic CYP and its redox partner. The structures with substrate and a series of reaction intermediates allow us to define the mechanism underlying sequential hydroxylations of the cholesterol and suggest the mechanism of C-C bond cleavage. In the complex the [2Fe-2S] cluster of Adx is positioned 17.4 A away from the heme iron of CYP11A1. This structure suggests that after an initial protein-protein association driven by electrostatic forces, the complex adopts an optimized geometry between the redox centers. Conservation of the interaction interface suggests that this mechanism is common for all mitochondrial P450s. | |||
Structural basis for pregnenolone biosynthesis by the mitochondrial monooxygenase system.,Strushkevich N, Mackenzie F, Cherkesova T, Grabovec I, Usanov S, Park HW Proc Natl Acad Sci U S A. 2011 Jun 2. PMID:21636783<ref>PMID:21636783</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
==See Also== | ==See Also== | ||
*[[Ferredoxin|Ferredoxin]] | *[[Ferredoxin|Ferredoxin]] | ||
== References == | |||
== | <references/> | ||
< | __TOC__ | ||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Arrowsmith, C H | [[Category: Arrowsmith, C H]] | ||
[[Category: Botchkarev, A | [[Category: Botchkarev, A]] | ||
[[Category: Bountra, C | [[Category: Bountra, C]] | ||
[[Category: Edwards, A M | [[Category: Edwards, A M]] | ||
[[Category: MacKenzie, F | [[Category: MacKenzie, F]] | ||
[[Category: Park, H | [[Category: Park, H]] | ||
[[Category: | [[Category: Structural genomic]] | ||
[[Category: Strushkevich, N V | [[Category: Strushkevich, N V]] | ||
[[Category: Tempel, W | [[Category: Tempel, W]] | ||
[[Category: Weigelt, J U | [[Category: Weigelt, J U]] | ||
[[Category: 22-dihydroxycholesterol]] | [[Category: 22-dihydroxycholesterol]] | ||
[[Category: Cytochrome p450]] | [[Category: Cytochrome p450]] | ||
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[[Category: Sgc]] | [[Category: Sgc]] | ||
[[Category: Side chain cleavage]] | [[Category: Side chain cleavage]] | ||
Revision as of 11:43, 9 December 2014
Crystal structure of human CYP11A1 in complex with 20,22-dihydroxycholesterolCrystal structure of human CYP11A1 in complex with 20,22-dihydroxycholesterol
Structural highlights
Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedIn humans, the precursor to all steroid hormones, pregnenolone, is synthesized from cholesterol by an enzyme complex comprising adrenodoxin reductase (AdR), adrenodoxin (Adx), and a cytochrome P450 (P450scc or CYP11A1). This complex not only plays a key role in steroidogenesis, but also has long been a model to study electron transfer, multistep catalysis, and C-C bond cleavage performed by monooxygenases. Detailed mechanistic understanding of these processes has been hindered by a lack of structural information. Here we present the crystal structure of the complex of human Adx and CYP11A1-the first of a complex between a eukaryotic CYP and its redox partner. The structures with substrate and a series of reaction intermediates allow us to define the mechanism underlying sequential hydroxylations of the cholesterol and suggest the mechanism of C-C bond cleavage. In the complex the [2Fe-2S] cluster of Adx is positioned 17.4 A away from the heme iron of CYP11A1. This structure suggests that after an initial protein-protein association driven by electrostatic forces, the complex adopts an optimized geometry between the redox centers. Conservation of the interaction interface suggests that this mechanism is common for all mitochondrial P450s. Structural basis for pregnenolone biosynthesis by the mitochondrial monooxygenase system.,Strushkevich N, Mackenzie F, Cherkesova T, Grabovec I, Usanov S, Park HW Proc Natl Acad Sci U S A. 2011 Jun 2. PMID:21636783[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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