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1h5z
From Proteopedia
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| - | [[Image:1h5z.gif|left|200px]]<br /><applet load="1h5z" size="350" color="white" frame="true" align="right" spinBox="true" | ||
| - | caption="1h5z, resolution 2.05Å" /> | ||
| - | '''CYTOCHROME P450 14 ALPHA-STEROL DEMETHYLASE (CYP51) FROM MYCOBACTERIUM TUBERCULOSIS IN FERRIC LOW-SPIN STATE'''<br /> | ||
| - | == | + | ==CYTOCHROME P450 14 ALPHA-STEROL DEMETHYLASE (CYP51) FROM MYCOBACTERIUM TUBERCULOSIS IN FERRIC LOW-SPIN STATE== |
| - | Sterol 14alpha-demethylases (CYP51) are essential enzymes in sterol | + | <StructureSection load='1h5z' size='340' side='right'caption='[[1h5z]], [[Resolution|resolution]] 2.05Å' scene=''> |
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[1h5z]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1H5Z OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1H5Z FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.05Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FE2:FE+(II)+ION'>FE2</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene></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=1h5z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1h5z OCA], [https://pdbe.org/1h5z PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1h5z RCSB], [https://www.ebi.ac.uk/pdbsum/1h5z PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1h5z ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/CP51_MYCTU CP51_MYCTU] Its precise biological substrate is not known. Catalyzes C14-demethylation of lanosterol, 24,25-dihydrolanosterol and obtusifoliol which is critical for ergosterol biosynthesis. It transforms lanosterol into 4,4'-dimethyl cholesta-8,14,24-triene-3-beta-ol.<ref>PMID:9756611</ref> <ref>PMID:10430874</ref> | ||
| + | == Evolutionary Conservation == | ||
| + | [[Image:Consurf_key_small.gif|200px|right]] | ||
| + | Check<jmol> | ||
| + | <jmolCheckbox> | ||
| + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/h5/1h5z_consurf.spt"</scriptWhenChecked> | ||
| + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
| + | <text>to colour the structure by Evolutionary Conservation</text> | ||
| + | </jmolCheckbox> | ||
| + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1h5z ConSurf]. | ||
| + | <div style="clear:both"></div> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Sterol 14alpha-demethylases (CYP51) are essential enzymes in sterol biosynthesis in eukaryotes and drug targets in antifungal therapy. Here, we report CYP51 structures in ligand-free and estriol bound forms. Using estriol as a probe, we determined orientation of the substrate in the active site, elucidated protein contacts with the invariant 3beta-hydroxy group of a sterol, and identified F78 as a key discriminator between 4alpha-methylated and 4alpha,beta-dimethylated substrates. Analysis of CYP51 dynamics revealed that the C helix undergoes helix-coil transition upon binding and dissociation of a ligand. Loss of helical structure of the C helix in the ligand-free form results in an unprecedented opening of the substrate binding site. Upon binding of estriol, the BC loop loses contacts with molecular surface and tends to adopt a closed conformation. A mechanism for azole resistance in the yeast pathogen Candida albicans associated with mutations in the ERG11 gene encoding CYP51 is suggested based on CYP51 protein dynamics. | ||
| - | + | Estriol bound and ligand-free structures of sterol 14alpha-demethylase.,Podust LM, Yermalitskaya LV, Lepesheva GI, Podust VN, Dalmasso EA, Waterman MR Structure. 2004 Nov;12(11):1937-45. PMID:15530358<ref>PMID:15530358</ref> | |
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| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | <div class="pdbe-citations 1h5z" style="background-color:#fffaf0;"></div> | |
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| - | + | ==See Also== | |
| + | *[[Cytochrome P450 3D structures|Cytochrome P450 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Mycobacterium tuberculosis]] | ||
| + | [[Category: Arase M]] | ||
| + | [[Category: Podust LM]] | ||
| + | [[Category: Waterman MR]] | ||
Current revision
CYTOCHROME P450 14 ALPHA-STEROL DEMETHYLASE (CYP51) FROM MYCOBACTERIUM TUBERCULOSIS IN FERRIC LOW-SPIN STATE
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