View source for 7jmt


==Crystal structure of schistosome BCL-2 bound to ABT-737==
<StructureSection load='7jmt' size='340' side='right'caption='[[7jmt]], [[Resolution|resolution]] 2.75&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7jmt]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Schistosoma_japonicum Schistosoma japonicum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7JMT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7JMT 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]] 2.75&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=N3C:4-{4-[(4-CHLOROBIPHENYL-2-YL)METHYL]PIPERAZIN-1-YL}-N-{[4-({(1R)-3-(DIMETHYLAMINO)-1-[(PHENYLTHIO)METHYL]PROPYL}AMINO)-3-NITROPHENYL]SULFONYL}BENZAMIDE'>N3C</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=7jmt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7jmt OCA], [https://pdbe.org/7jmt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7jmt RCSB], [https://www.ebi.ac.uk/pdbsum/7jmt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7jmt ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/A0A4Z2CSJ3_SCHJA A0A4Z2CSJ3_SCHJA] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Limited therapeutic options are available for the treatment of human schistosomiasis caused by the parasitic Schistosoma flatworm. The B cell lymphoma-2 (BCL-2)-regulated apoptotic cell death pathway in schistosomes was recently characterized and shown to share similarities with the intrinsic apoptosis pathway in humans. Here, we exploit structural differences in the human and schistosome BCL-2 (sBCL-2) pro-survival proteins toward a novel treatment strategy for schistosomiasis. The benzothiazole hydrazone scaffold previously employed to target human BCL-XL was repurposed as a starting point to target sBCL-2. We utilized X-ray structural data to inform optimization and then applied a scaffold-hop strategy to identify the 5-carboxamide thiazole hydrazone scaffold (43) with potent sBCL-2 activity (IC50 30 nM). Human BCL-XL potency (IC50 13 nM) was inadvertently preserved during the optimization process. The lead analogues from this study exhibit on-target activity in model fibroblast cell lines dependent on either sBCL-2 or human BCL-XL for survival. Further optimization of the thiazole hydrazone class is required to exhibit activity in schistosomes and enhance the potential of this strategy for treating schistosomiasis.

Optimization of Benzothiazole and Thiazole Hydrazones as Inhibitors of Schistosome BCL-2.,Nguyen W, Lee EF, Evangelista M, Lee M, Harris TJ, Colman PM, Smith NA, Williams LB, Jarman KE, Lowes KN, Haeberli C, Keiser J, Smith BJ, Fairlie WD, Sleebs BE ACS Infect Dis. 2021 Feb 1. doi: 10.1021/acsinfecdis.0c00700. PMID:33523649<ref>PMID:33523649</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7jmt" style="background-color:#fffaf0;"></div>

==See Also==
*[[B-cell lymphoma proteins 3D structures|B-cell lymphoma proteins 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Schistosoma japonicum]]
[[Category: Colman PM]]
[[Category: Fairlie WD]]
[[Category: Lee EF]]
[[Category: Smith BJ]]
[[Category: Smith NA]]