3ld6: Difference between revisions
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==Crystal structure of human lanosterol 14alpha-demethylase (CYP51) in complex with ketoconazole== | ==Crystal structure of human lanosterol 14alpha-demethylase (CYP51) in complex with ketoconazole== | ||
<StructureSection load='3ld6' size='340' side='right' caption='[[3ld6]], [[Resolution|resolution]] 2.80Å' scene=''> | <StructureSection load='3ld6' size='340' side='right' caption='[[3ld6]], [[Resolution|resolution]] 2.80Å' scene=''> | ||
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CYP51, CYP51A1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CYP51, CYP51A1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | ||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Sterol_14-demethylase Sterol 14-demethylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.13.70 1.14.13.70] </span></td></tr> | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Sterol_14-demethylase Sterol 14-demethylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.13.70 1.14.13.70] </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=3ld6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ld6 OCA], [http://pdbe.org/3ld6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3ld6 RCSB], [http://www.ebi.ac.uk/pdbsum/3ld6 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=3ld6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ld6 OCA], [http://pdbe.org/3ld6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3ld6 RCSB], [http://www.ebi.ac.uk/pdbsum/3ld6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3ld6 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
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Check<jmol> | Check<jmol> | ||
<jmolCheckbox> | <jmolCheckbox> | ||
<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ld/3ld6_consurf.spt"</scriptWhenChecked> | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ld/3ld6_consurf.spt"</scriptWhenChecked> | ||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
<text>to colour the structure by Evolutionary Conservation</text> | <text>to colour the structure by Evolutionary Conservation</text> | ||
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[[Category: Tempel, W]] | [[Category: Tempel, W]] | ||
[[Category: Weigelt, J]] | [[Category: Weigelt, J]] | ||
[[Category: Alternative splicing]] | |||
[[Category: Cholesterol biosynthesis]] | [[Category: Cholesterol biosynthesis]] | ||
[[Category: Cytochrome p450]] | [[Category: Cytochrome p450]] | ||
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[[Category: Nadp]] | [[Category: Nadp]] | ||
[[Category: Oxidoreductase]] | [[Category: Oxidoreductase]] | ||
[[Category: Polymorphism]] | |||
[[Category: Sgc]] | [[Category: Sgc]] | ||
[[Category: Steroid biosynthesis]] | [[Category: Steroid biosynthesis]] | ||
Revision as of 22:25, 24 January 2018
Crystal structure of human lanosterol 14alpha-demethylase (CYP51) in complex with ketoconazoleCrystal structure of human lanosterol 14alpha-demethylase (CYP51) in complex with ketoconazole
Structural highlights
Function[CP51A_HUMAN] Catalyzes C14-demethylation of lanosterol; it transforms lanosterol into 4,4'-dimethyl cholesta-8,14,24-triene-3-beta-ol. 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 PubMedThe obligatory step in sterol biosynthesis in eukaryotes is demethylation of sterol precursors at the C14-position, which is catalyzed by CYP51 (sterol 14-alpha demethylase) in three sequential reactions. In mammals, the final product of the pathway is cholesterol, while important intermediates, meiosis-activating sterols, are produced by CYP51. Three crystal structures of human CYP51, ligand-free and complexed with antifungal drugs ketoconazole and econazole, were determined, allowing analysis of the molecular basis for functional conservation within the CYP51 family. Azole binding occurs mostly through hydrophobic interactions with conservative residues of the active site. The substantial conformational changes in the B' helix and F-G loop regions are induced upon ligand binding, consistent with the membrane nature of the protein and its substrate. The access channel is typical for mammalian sterol-metabolizing P450 enzymes, but is different from that observed in Mycobacterium tuberculosis CYP51. Comparison of the azole-bound structures provides insight into the relative binding affinities of human and bacterial P450 enzymes to ketoconazole and fluconazole, which can be useful for the rational design of antifungal compounds and specific modulators of human CYP51. Structural basis of human CYP51 inhibition by antifungal azoles.,Strushkevich N, Usanov SA, Park HW J Mol Biol. 2010 Apr 9;397(4):1067-78. Epub 2010 Feb 10. PMID:20149798[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)
OCA- Human
- Sterol 14-demethylase
- Arrowsmith, C H
- Bountra, C
- Edwards, A M
- MacKenzie, F
- Park, H
- Structural genomic
- Strushkevich, N
- Tempel, W
- Weigelt, J
- Alternative splicing
- Cholesterol biosynthesis
- Cytochrome p450
- Endoplasmic reticulum
- Heme
- Iron
- Ketoconazole
- Lipid synthesis
- Membrane
- Metal-binding
- Microsome
- Monooxygenase
- Nadp
- Oxidoreductase
- Polymorphism
- Sgc
- Steroid biosynthesis
- Sterol 14alpha-demethylase
- Sterol biosynthesis
- Transmembrane