7zno
From Proteopedia
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[7zno]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Zika_virus Zika virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7ZNO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7ZNO FirstGlance]. <br> | <table><tr><td colspan='2'>[[7zno]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Zika_virus Zika virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7ZNO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7ZNO FirstGlance]. <br> | ||
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=JQI:[( | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.7Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=JQI:[(1~{R})-1-[[(2~{S})-6-azanyl-2-[[(2~{S})-6-azanyl-2-[2-[3-(4-carbamimidamido-3-oxidanylidene-pentyl)phenyl]ethanoylamino]hexanoyl]amino]hexanoyl]amino]-3-methyl-butyl]boronic+acid'>JQI</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=7zno FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7zno OCA], [https://pdbe.org/7zno PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7zno RCSB], [https://www.ebi.ac.uk/pdbsum/7zno PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7zno 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=7zno FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7zno OCA], [https://pdbe.org/7zno PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7zno RCSB], [https://www.ebi.ac.uk/pdbsum/7zno PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7zno ProSAT]</span></td></tr> | ||
</table> | </table> | ||
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The Zika virus (ZIKV) remains a potential threat to the public health due to the lack of both an approved vaccination or a specific treatment. In this work, a series of peptidic inhibitors of the ZIKV protease with boroleucine as P1 residue was synthesized. The highest affinities with K(i) values down to 8 nM were observed for compounds with basic residues in both P2 and P3 position and at the N-terminus. The low potency of reference compounds containing leucine, leucine-amide or isopentylamide as P1 residue suggested a covalent binding mode of the boroleucine-derived inhibitors. This was finally proven by crystal structure determination of the most potent inhibitor from this series in complex with the ZIKV protease. | The Zika virus (ZIKV) remains a potential threat to the public health due to the lack of both an approved vaccination or a specific treatment. In this work, a series of peptidic inhibitors of the ZIKV protease with boroleucine as P1 residue was synthesized. The highest affinities with K(i) values down to 8 nM were observed for compounds with basic residues in both P2 and P3 position and at the N-terminus. The low potency of reference compounds containing leucine, leucine-amide or isopentylamide as P1 residue suggested a covalent binding mode of the boroleucine-derived inhibitors. This was finally proven by crystal structure determination of the most potent inhibitor from this series in complex with the ZIKV protease. | ||
| - | Boroleucine-Derived Covalent Inhibitors of the ZIKV Protease.,Braun NJ, Huber S, Schmacke LC, Heine A, Steinmetzer T ChemMedChem. | + | Boroleucine-Derived Covalent Inhibitors of the ZIKV Protease.,Braun NJ, Huber S, Schmacke LC, Heine A, Steinmetzer T ChemMedChem. 2023 Feb 1;18(3):e202200336. doi: 10.1002/cmdc.202200336. Epub 2022 , Nov 21. PMID:36325810<ref>PMID:36325810</ref> |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
Current revision
Crystal Structure of Unlinked NS2B_NS3 Protease from Zika Virus in Complex with Boronate Inhibitor MI-2270
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