6kk2: Difference between revisions
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<StructureSection load='6kk2' size='340' side='right'caption='[[6kk2]], [[Resolution|resolution]] 2.02Å' scene=''> | <StructureSection load='6kk2' size='340' side='right'caption='[[6kk2]], [[Resolution|resolution]] 2.02Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'> | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6KK2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6KK2 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]] 2.02Å</td></tr> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.02Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=D9U:1-[(10~{S},17~{S},20~{S})-17,20-bis(4-azanylbutyl)-4,9,16,19,22-pentakis(oxidanylidene)-3,8,15,18,21-pentazabicyclo[22.2.2]octacosa-1(27),24(28),25-trien-10-yl]guanidine'>D9U</scene></td></tr> | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=D9U:1-[(10~{S},17~{S},20~{S})-17,20-bis(4-azanylbutyl)-4,9,16,19,22-pentakis(oxidanylidene)-3,8,15,18,21-pentazabicyclo[22.2.2]octacosa-1(27),24(28),25-trien-10-yl]guanidine'>D9U</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=6kk2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6kk2 OCA], [https://pdbe.org/6kk2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6kk2 RCSB], [https://www.ebi.ac.uk/pdbsum/6kk2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6kk2 ProSAT]</span></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=6kk2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6kk2 OCA], [https://pdbe.org/6kk2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6kk2 RCSB], [https://www.ebi.ac.uk/pdbsum/6kk2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6kk2 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Quek JP]] | [[Category: Quek JP]] | ||
Latest revision as of 11:05, 17 October 2024
Crystal structure of Zika NS2B-NS3 protease with compound 2Crystal structure of Zika NS2B-NS3 protease with compound 2
Structural highlights
Publication Abstract from PubMedA series of cyclic active-site directed inhibitors of the NS2B-NS3 proteases from Zika- (ZIKV), West Nile- (WNV), and Dengue-4 (DENV4) viruses was designed. The most potent compounds contain a reversely incorporated d-lysine residue in P1 position, where its side chain is connected to the P2 backbone, its a-amino group is converted into a guanidine for interaction with the conserved Asp129 side chain in the S1 pocket, and its carboxyl group is used for cyclization to the P3 lysine residue via an appropriate linker segment. The most potent compounds inhibit the ZIKV protease with K i values between 1.5 - 5 nM. Crystal structures of seven ZIKV protease inhibitor complexes were determined to support the design of the inhibitors. The binding mode of these compounds also explains their high selectivity as NS2B-NS3 inhibitors, which possess a negligible inhibitory effect on trypsin-like serine proteases or furin-like proprotein convertases. Although the WNV and DENV4 proteases are less efficiently inhibited, a comparable ranking of the potencies was observed for all three flavivirins suggesting that this compound type could serve as pan-flaviviral protease inhibitors. Structure-based macrocyclization of substrate analog NS2B-NS3 protease inhibitors of Zika, West Nile and Dengue viruses.,Braun NJ, Quek JP, Huber S, Kouretova J, Rogge D, Lang-Henkel H, Cheong ZKE, Chew BLA, Heine A, Luo D, Steinmetzer T ChemMedChem. 2020 Jun 5. doi: 10.1002/cmdc.202000237. PMID:32501637[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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