View source for 4bjk


==CYP51 of Trypanosoma brucei bound to (S)-N-(3-(1H-indol-3-yl)-1-oxo-1- (pyridin-4-ylamino)propan-2-yl)-3,3'-difluoro-(1,1'-biphenyl)-4- carboxamide==
<StructureSection load='4bjk' size='340' side='right'caption='[[4bjk]], [[Resolution|resolution]] 2.67&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4bjk]] 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=4BJK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4BJK 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]] 2.67&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=18I:3,3-DIFLUORO-N-[(2S)-3-(1H-INDOL-3-YL)-1-OXO-1-(PYRIDIN-4-YLAMINO)PROPAN-2-YL]BIPHENYL-4-CARBOXAMIDE'>18I</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=4bjk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bjk OCA], [https://pdbe.org/4bjk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4bjk RCSB], [https://www.ebi.ac.uk/pdbsum/4bjk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4bjk ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q385E8_TRYB2 Q385E8_TRYB2] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
A new series of 4-aminopyridyl-based lead inhibitors targeting Trypanosoma cruzi CYP51 (TcCYP51) has been developed using structure-based drug design as well as structure-property relationship (SPR) analyses. The screening hit starting point, LP10 (KD &lt;/= 42 nM; EC50 = 0.65 muM), has been optimized to give the potential leads 14t, 27i, 27q, 27r, and 27t, which have low-nanomolar binding affinity to TcCYP51 and significant activity against T. cruzi amastigotes cultured in human myoblasts (EC50 = 14-18 nM for 27i and 27r). Many of the optimized compounds have improved microsome stability, and most are selective against human CYPs 1A2, 2D6, and 3A4 (&lt;50% inhibition at 1 muM). A rationale for the improvement in microsome stability and selectivity of inhibitors against human metabolic CYP enzymes is presented. In addition, the binding mode of 14t with the Trypanosoma brucei CYP51 (TbCYP51) orthologue has been characterized by X-ray structure analysis.

Rational Development of 4-Aminopyridyl-Based Inhibitors Targeting Trypanosoma cruzi CYP51 as Anti-Chagas Agents.,Choi JY, Calvet CM, Gunatilleke SS, Ruiz C, Cameron MD, McKerrow JH, Podust LM, Roush WR J Med Chem. 2013 Sep 30. PMID:24079662<ref>PMID:24079662</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4bjk" style="background-color:#fffaf0;"></div>

==See Also==
*[[Cytochrome P450 3D structures|Cytochrome P450 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Trypanosoma brucei]]
[[Category: Podust LM]]