6z4n: Difference between revisions
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==CRYSTAL STRUCTURE OF OASS COMPLEXED WITH UPAR INHIBITOR== | ==CRYSTAL STRUCTURE OF OASS COMPLEXED WITH UPAR INHIBITOR== | ||
<StructureSection load='6z4n' size='340' side='right'caption='[[6z4n]]' scene=''> | <StructureSection load='6z4n' size='340' side='right'caption='[[6z4n]], [[Resolution|resolution]] 1.20Å' 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=6Z4N OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6Z4N FirstGlance]. <br> | <table><tr><td colspan='2'>[[6z4n]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Salmonella_enterica_subsp._enterica_serovar_Typhimurium_str._LT2 Salmonella enterica subsp. enterica serovar Typhimurium str. LT2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6Z4N OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6Z4N 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=6z4n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6z4n OCA], [https://pdbe.org/6z4n PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6z4n RCSB], [https://www.ebi.ac.uk/pdbsum/6z4n PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6z4n ProSAT]</span></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]] 1.2Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CO:COBALT+(II)+ION'>CO</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PLP:PYRIDOXAL-5-PHOSPHATE'>PLP</scene>, <scene name='pdbligand=Q7B:(1~{S},2~{S})-1-[(4-methylphenyl)methyl]-2-phenyl-cyclopropane-1-carboxylic+acid'>Q7B</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=6z4n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6z4n OCA], [https://pdbe.org/6z4n PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6z4n RCSB], [https://www.ebi.ac.uk/pdbsum/6z4n PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6z4n ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/CYSK_SALTY CYSK_SALTY] Two cysteine synthase enzymes are found. Both catalyze the same reaction. Cysteine synthase B can also use thiosulfate in place of sulfide to give cysteine thiosulfonate as a product. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Antibacterial adjuvants are of great significance, since they allow the therapeutic dose of conventional antibiotics to be lowered and reduce the insurgence of antibiotic resistance. Herein, we report that an O-acetylserine sulfhydrylase (OASS) inhibitor can be used as a colistin adjuvant to treat infections caused by Gram-positive and Gram-negative pathogens. A compound that binds OASS with a nM dissociation constant was tested as an adjuvant of colistin against six critical pathogens responsible for infections spreading worldwide, Escherichia coli, Salmonella enterica serovar Typhimurium, Klebisiella pneumoniae, Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, and Staphylococcus pseudintermedius. The compound showed promising synergistic or additive activities against all of them. Knockout experiments confirmed the intracellular target engagement supporting the proposed mechanism of action. Moreover, compound toxicity was evaluated by means of its hemolytic activity against sheep defibrinated blood cells, showing a good safety profile. The 3D structure of the compound in complex with OASS was determined at 1.2 A resolution by macromolecular crystallography, providing for the first time structural insights about the nature of the interaction between the enzyme and this class of competitive inhibitors. Our results provide a robust proof of principle supporting OASS as a potential nonessential antibacterial target to develop a new class of adjuvants and the structural basis for further structure-activity relationship studies. | |||
Investigational Studies on a Hit Compound Cyclopropane-Carboxylic Acid Derivative Targeting O-Acetylserine Sulfhydrylase as a Colistin Adjuvant.,Annunziato G, Spadini C, Franko N, Storici P, Demitri N, Pieroni M, Flisi S, Rosati L, Iannarelli M, Marchetti M, Magalhaes J, Bettati S, Mozzarelli A, Cabassi CS, Campanini B, Costantino G ACS Infect Dis. 2021 Feb 12;7(2):281-292. doi: 10.1021/acsinfecdis.0c00378. Epub , 2021 Jan 29. PMID:33513010<ref>PMID:33513010</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6z4n" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Salmonella enterica subsp. enterica serovar Typhimurium str. LT2]] | |||
[[Category: Campanini B]] | [[Category: Campanini B]] | ||
[[Category: Demitri N]] | [[Category: Demitri N]] | ||
[[Category: Storici P]] | [[Category: Storici P]] | ||
Latest revision as of 13:41, 24 January 2024
CRYSTAL STRUCTURE OF OASS COMPLEXED WITH UPAR INHIBITOR
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