4coh
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of Trypanosoma cruzi CYP51 bound to the sulfonamide derivative of the 4-aminopyridyl-based inhibitor== | |
| + | <StructureSection load='4coh' size='340' side='right'caption='[[4coh]], [[Resolution|resolution]] 2.08Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[4coh]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Trypanosoma_cruzi Trypanosoma cruzi]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4COH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4COH 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]] 2.08Å</td></tr> | ||
| + | <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=T9H:2-FLUORANYL-N-[(2R)-3-(1H-INDOL-3-YL)-1-OXIDANYLIDENE-1-(PYRIDIN-4-YLAMINO)PROPAN-2-YL]-4-(4-THIOPHEN-2-YLSULFONYLPIPERAZIN-1-YL)BENZAMIDE'>T9H</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=4coh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4coh OCA], [https://pdbe.org/4coh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4coh RCSB], [https://www.ebi.ac.uk/pdbsum/4coh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4coh ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/CP51_TRYCC CP51_TRYCC] Catalyzes C14-demethylation of lanosterol which is critical for ergosterol biosynthesis. It transforms lanosterol into 4,4'-dimethyl cholesta-8,14,24-triene-3-beta-ol (By similarity). Favors C4 dimethylated substrates, the substrate preference order is 24-methylenedihydrolanosterol > 24,25-dihydrolanosterol > lanosterol > obtusifoliol > norlanosterol.<ref>PMID:16321980</ref> [UniProtKB:P0A512] | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Chagas disease is a chronic infection caused by the protozoan parasite Trypanosoma cruzi, manifested in progressive cardiomyopathy and/or gastrointestinal dysfunction. Therapeutic options to prevent or treat Chagas disease are limited. CYP51, the enzyme key to the biosynthesis of eukaryotic membrane sterols, is a validated drug target in both fungi and T. cruzi. Sulfonamide derivatives of 4-aminopyridyl-based inhibitors of T. cruzi CYP51 (TcCYP51), including the sub-nanomolar compound 3, have molecular structures distinct from other validated CYP51 inhibitors. They augment the biologically relevant chemical space of molecules targeting TcCYP51. In a 2.08 A X-ray structure, TcCYP51 is in a conformation that has been influenced by compound 3 and is distinct from the previously characterized ground-state conformation of CYP51 drug-target complexes. That the binding site was modulated in response to an incoming inhibitor for the first time characterizes TcCYP51 as a flexible target rather than a rigid template. | ||
| - | + | Expanding the Binding Envelope of CYP51 Inhibitors Targeting Trypanosoma cruzi with 4-Aminopyridyl-Based Sulfonamide Derivatives.,Vieira DF, Choi JY, Roush WR, Podust LM Chembiochem. 2014 Apr 25. doi: 10.1002/cbic.201402027. PMID:24771705<ref>PMID:24771705</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| + | </div> | ||
| + | <div class="pdbe-citations 4coh" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Cytochrome P450 3D structures|Cytochrome P450 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Trypanosoma cruzi]] | ||
| + | [[Category: Choi JY]] | ||
| + | [[Category: Podust LM]] | ||
| + | [[Category: Roush WR]] | ||
| + | [[Category: Vieira DF]] | ||
Current revision
Crystal structure of Trypanosoma cruzi CYP51 bound to the sulfonamide derivative of the 4-aminopyridyl-based inhibitor
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