View source for 7vxy


==Zika virus NS2B/NS3 protease bZipro(C143S) in complex with D-RKOR==
<StructureSection load='7vxy' size='340' side='right'caption='[[7vxy]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7vxy]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Zika_virus Zika virus] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7VXY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7VXY 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]] 1.901&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DAR:D-ARGININE'>DAR</scene>, <scene name='pdbligand=ORN:L-ORNITHINE'>ORN</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=7vxy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7vxy OCA], [https://pdbe.org/7vxy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7vxy RCSB], [https://www.ebi.ac.uk/pdbsum/7vxy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7vxy ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/H8XX12_ZIKV H8XX12_ZIKV] Peptide 2k: Functions as a signal peptide for NS4B and is required for the interferon antagonism activity of the latter.[SAAS:SAAS00882589]
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Zika virus (ZIKV) has been a serious public health problem, and there is no vaccine or drug approved for the prevention or treatment of ZIKV yet. The ZIKV NS2B/NS3 protease plays an important role in processing the virus precursor polyprotein and is thus a promising target for antiviral drugs development. In order to discover novel inhibitors of this protease, we carried out a fragment-based hit screening and characterized protein-inhibitor interactions using the X-ray crystallography together with isothermal titration calorimetry. We reported two high-resolution crystal structures of the protease (bZiPro(C143S)) in complex with an active fragment as well as a tetrapeptide, revealing that there is domain swapping in the protein structures and two ligands only occupy the substrate-binding pocket of one copy in a symmetric unit. Based on the detailed binding modes of two ligands revealed by crystal structures, we designed a novel inhibitor which inhibits the NS2B/NS3 protease with a higher potency than the fragment and possesses a higher ligand-binding efficiency and a comparable IC50 compared to the tetrapeptide. These results thus provide a structural basis and valuable hint for development of more potent inhibitors of the ZIKV NS2B/NS3 protease.

Structure-based design of a novel inhibitor of the ZIKA virus NS2B/NS3 protease.,Xiong Y, Cheng F, Zhang J, Su H, Hu H, Zou Y, Li M, Xu Y Bioorg Chem. 2022 Nov;128:106109. doi: 10.1016/j.bioorg.2022.106109. Epub 2022, Aug 25. PMID:36049322<ref>PMID:36049322</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7vxy" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Synthetic construct]]
[[Category: Zika virus]]
[[Category: Cheng F]]
[[Category: Hu HC]]
[[Category: Li MJ]]
[[Category: Su HX]]
[[Category: Xiong YC]]
[[Category: Xu YC]]
[[Category: Zhang JY]]
[[Category: Zou Y]]