7oc7
From Proteopedia
(Difference between revisions)
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==LasB, alpha-alkyl-N-aryl mercaptoacetamide== | ==LasB, alpha-alkyl-N-aryl mercaptoacetamide== | ||
| - | <StructureSection load='7oc7' size='340' side='right'caption='[[7oc7]]' scene=''> | + | <StructureSection load='7oc7' size='340' side='right'caption='[[7oc7]], [[Resolution|resolution]] 1.95Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7OC7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7OC7 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7oc7]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7OC7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7OC7 FirstGlance]. <br> |
| - | </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=7oc7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7oc7 OCA], [https://pdbe.org/7oc7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7oc7 RCSB], [https://www.ebi.ac.uk/pdbsum/7oc7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7oc7 ProSAT]</span></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=V85:(2R)-N,3-diphenyl-2-sulfanyl-propanamide'>V85</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=7oc7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7oc7 OCA], [https://pdbe.org/7oc7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7oc7 RCSB], [https://www.ebi.ac.uk/pdbsum/7oc7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7oc7 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Function == | ||
| + | [[https://www.uniprot.org/uniprot/Q3Y6H8_PSEAI Q3Y6H8_PSEAI]] Extracellular zinc metalloprotease.[RuleBase:RU366073] | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Extracellular virulence factors have emerged as attractive targets in the current antimicrobial resistance crisis. The Gram-negative pathogen Pseudomonas aeruginosa secretes the virulence factor elastase B (LasB), which plays an important role in the infection process. Here, we report a sub-micromolar, non-peptidic, fragment-like inhibitor of LasB discovered by careful visual inspection of structural data. Inspired by the natural LasB substrate, the original fragment was successfully merged and grown. The optimized inhibitor is accessible via simple chemistry and retained selectivity with a substantial improvement in activity, which can be rationalized by the crystal structure of LasB in complex with the inhibitor. We also demonstrate an improved in vivo efficacy of the optimized hit in Galleria mellonella larvae, highlighting the significance of this class of compounds as promising drug candidates. | ||
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| + | Substrate-Inspired Fragment Merging and Growing Affords Efficacious LasB Inhibitors.,Kaya C, Walter I, Yahiaoui S, Sikandar A, Alhayek A, Konstantinovic J, Kany AM, Haupenthal J, Kohnke J, Hartmann RW, Hirsch AKH Angew Chem Int Ed Engl. 2022 Jan 26;61(5):e202112295. doi:, 10.1002/anie.202112295. Epub 2021 Dec 13. PMID:34762767<ref>PMID:34762767</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7oc7" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: Koehnke J]] | + | [[Category: Koehnke, J]] |
| - | [[Category: Sikandar A]] | + | [[Category: Sikandar, A]] |
| + | [[Category: Alpha-alkyl-n-aryl mercaptoacetamide]] | ||
| + | [[Category: Hydrolase]] | ||
| + | [[Category: Lasb]] | ||
Revision as of 07:10, 27 January 2022
LasB, alpha-alkyl-N-aryl mercaptoacetamide
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