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3p99

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==Sterol 14alpha-demethylase (CYP51) from Trypanosoma brucei in complex with delta7-14alpha-methylene-cyclopropyl-dihydrolanosterol==
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The line below this paragraph, containing "STRUCTURE_3p99", creates the "Structure Box" on the page.
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<StructureSection load='3p99' size='340' side='right'caption='[[3p99]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[3p99]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Trypanosoma_brucei Trypanosoma brucei]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3P99 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3P99 FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=LNP:(3ALPHA,9BETA,10ALPHA,13ALPHA)-30-CYCLOPROPYLIDENELANOST-7-EN-3-OL'>LNP</scene></td></tr>
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{{STRUCTURE_3p99| PDB=3p99 | SCENE= }}
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3p99 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3p99 OCA], [https://pdbe.org/3p99 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3p99 RCSB], [https://www.ebi.ac.uk/pdbsum/3p99 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3p99 ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/Q385E8_TRYB2 Q385E8_TRYB2]
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Sterol 14alpha-demethylase (CYP51) that catalyzes the removal of the 14alpha-methyl group from the sterol nucleus is an essential enzyme in sterol biosynthesis, a primary target for clinical and agricultural antifungal azoles and an emerging target for antitrypanosomal chemotherapy. Here, we present the crystal structure of Trypanosoma (T) brucei CYP51 in complex with the substrate analog 14alpha-methylenecyclopropyl-Delta7-24,25-dihydrolanosterol (MCP). This sterol binds tightly to all protozoan CYP51s and acts as a competitive inhibitor of F105-containing (plant-like) T. brucei and Leishmania (L) infantum orthologs, but it has a much stronger, mechanism-based inhibitory effect on I105-containing (animal/fungi-like) T. cruzi CYP51. Depicting substrate orientation in the conserved CYP51 binding cavity, the complex specifies the roles of the contact amino acid residues and sheds new light on CYP51 substrate specificity. It also provides an explanation for the effect of MCP on T. cruzi CYP51. Comparison with the ligand-free and azole-bound structures supports the notion of structural rigidity as the characteristic feature of the CYP51 substrate binding cavity, confirming the enzyme as an excellent candidate for structure-directed design of new drugs, including mechanism-based substrate analog inhibitors.
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===Sterol 14alpha-demethylase (CYP51) from Trypanosoma brucei in complex with delta7-14alpha-methylene-cyclopropyl-dihydrolanosterol===
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Structural complex of sterol 14alpha-demethylase (CYP51) with 14alpha-methylenecyclopropyl-Delta7-24, 25-dihydrolanosterol.,Hargrove TY, Wawrzak Z, Liu J, Waterman MR, Nes WD, Lepesheva GI J Lipid Res. 2012 Feb;53(2):311-20. Epub 2011 Nov 30. PMID:22135275<ref>PMID:22135275</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 3p99" style="background-color:#fffaf0;"></div>
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==About this Structure==
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==See Also==
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[[3p99]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Trypanosoma_brucei Trypanosoma brucei]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3P99 OCA].
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*[[Cytochrome P450 3D structures|Cytochrome P450 3D structures]]
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[[Category: Sterol 14-demethylase]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Large Structures]]
[[Category: Trypanosoma brucei]]
[[Category: Trypanosoma brucei]]
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[[Category: Hargrove, T Y.]]
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[[Category: Hargrove TY]]
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[[Category: Lepesheva, G I.]]
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[[Category: Lepesheva GI]]
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[[Category: Waterman, M R]]
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[[Category: Waterman MR]]
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[[Category: Wawrzak, Z.]]
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[[Category: Wawrzak Z]]
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[[Category: Cyp51]]
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[[Category: Cytochrome p450 fold/sterol 14-alpha demethylase]]
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[[Category: Endoplasmic reticulum]]
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[[Category: Hemoprotein]]
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[[Category: Membrane]]
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[[Category: Monooxygenase]]
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[[Category: Oxidoreductase]]
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[[Category: Sterol biosynthesis]]
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Current revision

Sterol 14alpha-demethylase (CYP51) from Trypanosoma brucei in complex with delta7-14alpha-methylene-cyclopropyl-dihydrolanosterol

PDB ID 3p99

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