4u2s: Difference between revisions
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<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=4u2s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4u2s OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4u2s RCSB], [http://www.ebi.ac.uk/pdbsum/4u2s PDBsum]</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=4u2s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4u2s OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4u2s RCSB], [http://www.ebi.ac.uk/pdbsum/4u2s PDBsum]</span></td></tr> | ||
</table> | </table> | ||
== Function == | |||
[[http://www.uniprot.org/uniprot/CHOD_STRS0 CHOD_STRS0]] Bifunctional enzyme that catalyzes the oxidation of the 3-beta-hydroxy group of cholesterol and the isomerization of the double bond of the resulting product. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Cholesterol oxidase (CO) is a flavoenzyme that catalyzes the oxidation and isomerization of cholesterol to cholest-4-en-3-one. The reductive half reaction occurs via a hydride transfer from the substrate to the FAD cofactor. The structures of CO reduced with dithionite under aerobic conditions and in the presence of the substrate 2-propanol under both aerobic and anaerobic conditions are presented. The 1.32 A resolution structure of the dithionite-reduced enzyme reveals a sulfite molecule covalently bound to the FAD cofactor. The isoalloxazine ring system displays a bent structure relative to that of the oxidized enzyme, and alternate conformations of a triad of aromatic residues near to the cofactor are evident. A 1.12 A resolution anaerobically trapped reduced enzyme structure in the presence of 2-propanol does not show a similar bending of the flavin ring system, but does show alternate conformations of the aromatic triad. Additionally, a significant difference electron-density peak is observed within a covalent-bond distance of N5 of the flavin moiety, suggesting that a hydride-transfer event has occurred as a result of substrate oxidation trapping the flavin in the electron-rich reduced state. The hydride transfer generates a tetrahedral geometry about the flavin N5 atom. High-level density-functional theory calculations were performed to correlate the crystallographic findings with the energetics of this unusual arrangement of the flavin moiety. These calculations suggest that strong hydrogen-bond interactions between Gly120 and the flavin N5 centre may play an important role in these structural features. | |||
High-resolution structures of cholesterol oxidase in the reduced state provide insights into redox stabilization.,Golden E, Karton A, Vrielink A Acta Crystallogr D Biol Crystallogr. 2014 Dec 1;70(Pt 12):3155-66. doi:, 10.1107/S139900471402286X. Epub 2014 Nov 22. PMID:25478834<ref>PMID:25478834</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Revision as of 13:48, 24 December 2014
Cholesterol oxidase in the reduced state complexed with isopropanolCholesterol oxidase in the reduced state complexed with isopropanol
Structural highlights
Function[CHOD_STRS0] Bifunctional enzyme that catalyzes the oxidation of the 3-beta-hydroxy group of cholesterol and the isomerization of the double bond of the resulting product. Publication Abstract from PubMedCholesterol oxidase (CO) is a flavoenzyme that catalyzes the oxidation and isomerization of cholesterol to cholest-4-en-3-one. The reductive half reaction occurs via a hydride transfer from the substrate to the FAD cofactor. The structures of CO reduced with dithionite under aerobic conditions and in the presence of the substrate 2-propanol under both aerobic and anaerobic conditions are presented. The 1.32 A resolution structure of the dithionite-reduced enzyme reveals a sulfite molecule covalently bound to the FAD cofactor. The isoalloxazine ring system displays a bent structure relative to that of the oxidized enzyme, and alternate conformations of a triad of aromatic residues near to the cofactor are evident. A 1.12 A resolution anaerobically trapped reduced enzyme structure in the presence of 2-propanol does not show a similar bending of the flavin ring system, but does show alternate conformations of the aromatic triad. Additionally, a significant difference electron-density peak is observed within a covalent-bond distance of N5 of the flavin moiety, suggesting that a hydride-transfer event has occurred as a result of substrate oxidation trapping the flavin in the electron-rich reduced state. The hydride transfer generates a tetrahedral geometry about the flavin N5 atom. High-level density-functional theory calculations were performed to correlate the crystallographic findings with the energetics of this unusual arrangement of the flavin moiety. These calculations suggest that strong hydrogen-bond interactions between Gly120 and the flavin N5 centre may play an important role in these structural features. High-resolution structures of cholesterol oxidase in the reduced state provide insights into redox stabilization.,Golden E, Karton A, Vrielink A Acta Crystallogr D Biol Crystallogr. 2014 Dec 1;70(Pt 12):3155-66. doi:, 10.1107/S139900471402286X. Epub 2014 Nov 22. PMID:25478834[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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