2q9g: Difference between revisions
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CYP46A1, CYP46 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr> | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CYP46A1, CYP46 ([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_24-hydroxylase Cholesterol 24-hydroxylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.13.98 1.14.13.98] </span></td></tr> | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Cholesterol_24-hydroxylase Cholesterol 24-hydroxylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.13.98 1.14.13.98] </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=2q9g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2q9g OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2q9g RCSB], [http://www.ebi.ac.uk/pdbsum/2q9g 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=2q9g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2q9g OCA], [http://pdbe.org/2q9g PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2q9g RCSB], [http://www.ebi.ac.uk/pdbsum/2q9g PDBsum]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 2q9g" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
Revision as of 11:38, 10 September 2015
Crystal structure of human cytochrome P450 46A1Crystal structure of human cytochrome P450 46A1
Structural highlights
Function[CP46A_HUMAN] Involved in the turnover of cholesterol. It converts cholesterol into 24S-hydroxycholesterol and, to a lesser extent, 25-hydroxycholesterol. 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 PubMedBy converting cholesterol to 24S-hydroxycholesterol, cytochrome P450 46A1 (CYP46A1) initiates the major pathway for cholesterol removal from the brain. Two crystal structures of CYP46A1 were determined. First is the 1.9-A structure of CYP46A1 complexed with a high-affinity substrate cholesterol 3-sulfate (CH-3S). The second structure is that of the substrate-free CYP46A1 at 2.4-A resolution. CH-3S is bound in the productive orientation and occupies the entire length of the banana-shaped hydrophobic active-site cavity. A unique helix B'-C loop insertion (residues 116-120) contributes to positioning cholesterol for oxygenation catalyzed by CYP46A1. A comparison with the substrate-free structure reveals substantial substrate-induced conformational changes in CYP46A1 and suggests that structurally distinct compounds could bind in the enzyme active site. In vitro assays were performed to characterize the effect of different therapeutic agents on cholesterol hydroxylase activity of purified full-length recombinant CYP46A1, and several strong inhibitors and modest coactivators of CYP46A1 were identified. Structural and biochemical data provide evidence that CYP46A1 activity could be altered by exposure to some therapeutic drugs and potentially other xenobiotics. Crystal structures of substrate-bound and substrate-free cytochrome P450 46A1, the principal cholesterol hydroxylase in the brain.,Mast N, White MA, Bjorkhem I, Johnson EF, Stout CD, Pikuleva IA Proc Natl Acad Sci U S A. 2008 Jul 15;105(28):9546-51. Epub 2008 Jul 9. PMID:18621681[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences |
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