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4qck

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==Crystal structure of 3-ketosteroid-9-alpha-hydroxylase (KshA) from M. tuberculosis in complex with 4-androstene-3,17-dione==
==Crystal structure of 3-ketosteroid-9-alpha-hydroxylase (KshA) from M. tuberculosis in complex with 4-androstene-3,17-dione==
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<StructureSection load='4qck' size='340' side='right' caption='[[4qck]], [[Resolution|resolution]] 2.46&Aring;' scene=''>
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<StructureSection load='4qck' size='340' side='right'caption='[[4qck]], [[Resolution|resolution]] 2.46&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[4qck]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4QCK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4QCK FirstGlance]. <br>
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<table><tr><td colspan='2'>[[4qck]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_H37Rv Mycobacterium tuberculosis H37Rv]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4QCK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4QCK FirstGlance]. <br>
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</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ASD:4-ANDROSTENE-3-17-DIONE'>ASD</scene>, <scene name='pdbligand=FE:FE+(III)+ION'>FE</scene>, <scene name='pdbligand=FES:FE2/S2+(INORGANIC)+CLUSTER'>FES</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene><br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.46&#8491;</td></tr>
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<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4qdc|4qdc]], [[4qdd|4qdd]], [[4qdf|4qdf]]</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ASD:4-ANDROSTENE-3-17-DIONE'>ASD</scene>, <scene name='pdbligand=FE:FE+(III)+ION'>FE</scene>, <scene name='pdbligand=FES:FE2/S2+(INORGANIC)+CLUSTER'>FES</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
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<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/3-ketosteroid_9-alpha-monooxygenase 3-ketosteroid 9-alpha-monooxygenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.13.142 1.14.13.142] </span></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4qck FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qck OCA], [https://pdbe.org/4qck PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4qck RCSB], [https://www.ebi.ac.uk/pdbsum/4qck PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4qck ProSAT]</span></td></tr>
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<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4qck FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qck OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4qck RCSB], [http://www.ebi.ac.uk/pdbsum/4qck PDBsum]</span></td></tr>
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</table>
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<table>
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== Function ==
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<div style="background-color:#fffaf0;">
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[https://www.uniprot.org/uniprot/KSHA_MYCTU KSHA_MYCTU] Catalyzes the opening of ring B of 1,4-androstadiene-3,17,-dione (ADD) and 4-androstene-3,17-dione (ADD) with concomitant aromatization of ring A. The ring B is subsequently hydroxylated to yield a catechol and then subject to meta-cleavage.
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== Publication Abstract from PubMed ==
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KshA is the oxygenase component of 3-ketosteroid 9alpha-hydroxylase, a Rieske oxygenase involved in the bacterial degradation of steroids. Consistent with its role in bile acid catabolism, KshA1 from Rhodococcus rhodochrous DSM43269 had the highest apparent specificity (kcat/Km) for steroids with an isopropyl side chain at C17, such as 3-oxo-23,24-bisnorcholesta-1,4-diene-22-oate (1,4-BNC). By contrast, the KshA5 homolog had the highest apparent specificity for substrates with no C17 side chain (kcat/Km &gt;10(5) s(-1) m(-1) for 4-estrendione, 5alpha-androstandione, and testosterone). Unexpectedly, substrates such as 4-androstene-3,17-dione (ADD) and 4-BNC displayed strong substrate inhibition (Ki S approximately 100 mum). By comparison, the cholesterol-degrading KshAMtb from Mycobacterium tuberculosis had the highest specificity for CoA-thioesterified substrates. These specificities are consistent with differences in the catabolism of cholesterol and bile acids, respectively, in actinobacteria. X-ray crystallographic structures of the KshAMtb.ADD, KshA1.1,4-BNC-CoA, KshA5.ADD, and KshA5.1,4-BNC-CoA complexes revealed that the enzymes have very similar steroid-binding pockets with the substrate's C17 oriented toward the active site opening. Comparisons suggest Tyr-245 and Phe-297 are determinants of KshA1 specificity. All enzymes have a flexible 16-residue "mouth loop," which in some structures completely occluded the substrate-binding pocket from the bulk solvent. Remarkably, the catalytic iron and alpha-helices harboring its ligands were displaced up to 4.4 A in the KshA5.substrate complexes as compared with substrate-free KshA, suggesting that Rieske oxygenases may have a dynamic nature similar to cytochrome P450.
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Substrate specificities and conformational flexibility of 3-ketosteroid 9alpha-hydroxylases.,Penfield JS, Worrall LJ, Strynadka NC, Eltis LD J Biol Chem. 2014 Sep 12;289(37):25523-36. doi: 10.1074/jbc.M114.575886. Epub, 2014 Jul 21. PMID:25049233<ref>PMID:25049233</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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== References ==
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<references/>
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: 3-ketosteroid 9-alpha-monooxygenase]]
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[[Category: Large Structures]]
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[[Category: Eltis, L D.]]
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[[Category: Mycobacterium tuberculosis H37Rv]]
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[[Category: Penfield, J.]]
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[[Category: Eltis LD]]
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[[Category: Strynadka, N C.]]
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[[Category: Penfield J]]
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[[Category: Worrall, L J.]]
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[[Category: Strynadka NC]]
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[[Category: Mixed function oxygenase]]
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[[Category: Worrall LJ]]
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[[Category: Oxidoreductase]]
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Current revision

Crystal structure of 3-ketosteroid-9-alpha-hydroxylase (KshA) from M. tuberculosis in complex with 4-androstene-3,17-dione

PDB ID 4qck

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