4coh: Difference between revisions
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==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 [http://en.wikipedia.org/wiki/Trycr Trycr]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4COH OCA]. <br> | |||
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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><br> | |||
<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Glucokinase Glucokinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.2 2.7.1.2] </span></td></tr> | |||
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4coh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4coh OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4coh RCSB], [http://www.ebi.ac.uk/pdbsum/4coh PDBsum]</span></td></tr> | |||
<table> | |||
<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> | |||
== References == | |||
== | <references/> | ||
<references | __TOC__ | ||
</StructureSection> | |||
[[Category: Sterol 14-demethylase]] | [[Category: Sterol 14-demethylase]] | ||
[[Category: Trycr]] | |||
[[Category: Choi, J Y.]] | [[Category: Choi, J Y.]] | ||
[[Category: Podust, L M.]] | [[Category: Podust, L M.]] | ||
Revision as of 10:01, 7 May 2014
Crystal structure of Trypanosoma cruzi CYP51 bound to the sulfonamide derivative of the 4-aminopyridyl-based inhibitorCrystal structure of Trypanosoma cruzi CYP51 bound to the sulfonamide derivative of the 4-aminopyridyl-based inhibitor
Structural highlights
Publication Abstract from PubMedChagas 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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