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4uvr
From Proteopedia
(Difference between revisions)
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| - | ''' | + | ==Binding mode, selectivity and potency of N-indolyl-oxopyridinyl-4- amino-propanyl-based inhibitors targeting Trypanosoma cruzi CYP51== |
| + | <StructureSection load='4uvr' size='340' side='right' caption='[[4uvr]], [[Resolution|resolution]] 2.48Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[4uvr]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4UVR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4UVR FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=J5Y:NALPHA-{4-[4-(5-CHLORO-2-METHYLPHENYL)PIPERAZIN-1-YL]-2-FLUOROBENZOYL}-N-PYRIDIN-4-YL-D-TRYPTOPHANAMIDE'>J5Y</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=4uvr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4uvr OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4uvr RCSB], [http://www.ebi.ac.uk/pdbsum/4uvr PDBsum]</span></td></tr> | ||
| + | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Chagas disease is a chronic infection in humans caused by Trypanosoma cruzi and manifested in progressive cardiomyopathy and/or gastrointestinal dysfunction. Limited therapeutic options to prevent and treat Chagas disease put 8 million people infected with T. cruzi worldwide at risk. CYP51, involved in the biosynthesis of the membrane sterol component in eukaryotes, is a promising drug target in T. cruzi. We report the structure-activity relationships (SAR) of an N-arylpiperazine series of N-indolyloxopyridinyl-4-aminopropanyl-based inhibitors designed to probe the impact of substituents in the terminal N-phenyl ring on binding mode, selectivity and potency. Depending on the substituents at C-4, two distinct ring binding modes, buried and solvent-exposed, have been observed by X-ray structure analysis (resolution of 1.95-2.48 A). The 5-chloro-substituted analogs 9 and 10 with no substituent at C-4 demonstrated improved selectivity and potency, suppressing >/=99.8% parasitemia in mice when administered orally at 25 mg/kg, b.i.d., for 4 days. | ||
| - | + | Binding Mode and Potency of N-Indolyloxopyridinyl-4-aminopropanyl-Based Inhibitors Targeting Trypanosoma cruzi CYP51.,Vieira DF, Choi JY, Calvet CM, Siqueira-Neto JL, Johnston JB, Kellar D, Gut J, Cameron MD, McKerrow JH, Roush WR, Podust LM J Med Chem. 2014 Nov 25. PMID:25393646<ref>PMID:25393646</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | == References == | |
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Sterol 14-demethylase]] | ||
| + | [[Category: Calvet, C M]] | ||
| + | [[Category: Choi, J Y]] | ||
| + | [[Category: Gut, J]] | ||
| + | [[Category: Johnston, J B]] | ||
| + | [[Category: Kellar, D]] | ||
| + | [[Category: McKerrow, J H]] | ||
| + | [[Category: Podust, L M]] | ||
| + | [[Category: Roush, W R]] | ||
| + | [[Category: Siqueira-Neto, J L]] | ||
| + | [[Category: Vieira, D F]] | ||
| + | [[Category: Chagas disease]] | ||
| + | [[Category: Cyp51]] | ||
| + | [[Category: Oxidoreductase]] | ||
| + | [[Category: Sterol biosynthesis]] | ||
Revision as of 07:50, 26 November 2014
Binding mode, selectivity and potency of N-indolyl-oxopyridinyl-4- amino-propanyl-based inhibitors targeting Trypanosoma cruzi CYP51
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