View source for 5ogq


==Structure of cathepsin B1 from Schistosoma mansoni in complex with WRR391 inhibitor==
<StructureSection load='5ogq' size='340' side='right'caption='[[5ogq]], [[Resolution|resolution]] 1.91&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5ogq]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Schistosoma_mansoni Schistosoma mansoni]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5OGQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5OGQ 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]] 1.91&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=9U8:ethyl+1-[[(2~{S})-3-(4-hydroxyphenyl)-1-oxidanylidene-1-[[(3~{S})-1-phenyl-5-pyridin-2-ylsulfonyl-pentan-3-yl]amino]propan-2-yl]carbamoyl]piperidine-4-carboxylate'>9U8</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</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=5ogq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ogq OCA], [https://pdbe.org/5ogq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ogq RCSB], [https://www.ebi.ac.uk/pdbsum/5ogq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ogq ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q8MNY2_SCHMA Q8MNY2_SCHMA] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Schistosomiasis, a parasitic disease caused by blood flukes of the genus Schistosoma, is a global health problem with over 200 million people infected. Treatment relies on just one drug, and new chemotherapies are needed. Schistosoma mansoni cathepsin B1 (SmCB1) is a critical peptidase for the digestion of host blood proteins and a validated drug target. We screened a library of peptidomimetic vinyl sulfones against SmCB1 and identified the most potent SmCB1 inhibitors reported to date that are active in the subnanomolar range with second order rate constants (k2nd) of approximately 2 x 10(5) M(-1) s(-1). High resolution crystal structures of the two best inhibitors in complex with SmCB1 were determined. Quantum chemical calculations of their respective binding modes identified critical hot spot interactions in the S1' and S2 subsites. The most potent inhibitor targets the S1' subsite with an N-hydroxysulfonic amide moiety and displays favorable functional properties, including bioactivity against the pathogen, selectivity for SmCB1 over human cathepsin B, and reasonable metabolic stability. Our results provide structural insights for the rational design of next-generation SmCB1 inhibitors as potential drugs to treat schistosomiasis.

Druggable Hot Spots in the Schistosomiasis Cathepsin B1 Target Identified by Functional and Binding Mode Analysis of Potent Vinyl Sulfone Inhibitors.,Jilkova A, Rubesova P, Fanfrlik J, Fajtova P, Rezacova P, Brynda J, Lepsik M, Mertlikova-Kaiserova H, Emal CD, Renslo AR, Roush WR, Horn M, Caffrey CR, Mares M ACS Infect Dis. 2020 Nov 11. doi: 10.1021/acsinfecdis.0c00501. PMID:33175511<ref>PMID:33175511</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5ogq" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Schistosoma mansoni]]
[[Category: Brynda J]]
[[Category: Jilkova A]]
[[Category: Mares M]]
[[Category: Rezacova P]]