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| | == Structural highlights == | | == Structural highlights == |
| | <table><tr><td colspan='2'>[[2q9g]] is a 1 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=2Q9G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2Q9G FirstGlance]. <br> | | <table><tr><td colspan='2'>[[2q9g]] is a 1 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=2Q9G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2Q9G FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2q9f|2q9f]]</div></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CYP46A1, CYP46 ([https://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'>[https://en.wikipedia.org/wiki/Cholesterol_24-hydroxylase Cholesterol 24-hydroxylase], with EC number [https://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'>[https://proteopedia.org/fgij/fg.htm?mol=2q9g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2q9g OCA], [https://pdbe.org/2q9g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2q9g RCSB], [https://www.ebi.ac.uk/pdbsum/2q9g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2q9g ProSAT]</span></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=2q9g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2q9g OCA], [https://pdbe.org/2q9g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2q9g RCSB], [https://www.ebi.ac.uk/pdbsum/2q9g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2q9g ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/CP46A_HUMAN CP46A_HUMAN]] Involved in the turnover of cholesterol. It converts cholesterol into 24S-hydroxycholesterol and, to a lesser extent, 25-hydroxycholesterol.
| + | [https://www.uniprot.org/uniprot/CP46A_HUMAN CP46A_HUMAN] Involved in the turnover of cholesterol. It converts cholesterol into 24S-hydroxycholesterol and, to a lesser extent, 25-hydroxycholesterol. |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Cholesterol 24-hydroxylase]] | |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Johnson, E F]] | + | [[Category: Johnson EF]] |
| - | [[Category: Mast, N V]] | + | [[Category: Mast NV]] |
| - | [[Category: Pikuleva, I A]] | + | [[Category: Pikuleva IA]] |
| - | [[Category: Stout, C D]] | + | [[Category: Stout CD]] |
| - | [[Category: White, M A]] | + | [[Category: White MA]] |
| - | [[Category: Cholesterol metabolic enzyme]]
| + | |
| - | [[Category: Cyp46a1]]
| + | |
| - | [[Category: Heme]]
| + | |
| - | [[Category: Monooxygenase]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| - | [[Category: P450]]
| + | |
| - | [[Category: 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 PubMed
By 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 Also
References
- ↑ Mast N, White MA, Bjorkhem I, Johnson EF, Stout CD, Pikuleva IA. Crystal structures of substrate-bound and substrate-free cytochrome P450 46A1, the principal cholesterol hydroxylase in the brain. Proc Natl Acad Sci U S A. 2008 Jul 15;105(28):9546-51. Epub 2008 Jul 9. PMID:18621681
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