View source for 6t60


==Crystal structure of Acinetobacter baumannii FabG at 1.66 A resolution==
<StructureSection load='6t60' size='340' side='right'caption='[[6t60]], [[Resolution|resolution]] 1.66&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6t60]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Acinetobacter_baumannii Acinetobacter baumannii]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6T60 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6T60 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]] 1.66&#8491;</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=6t60 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6t60 OCA], [https://pdbe.org/6t60 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6t60 RCSB], [https://www.ebi.ac.uk/pdbsum/6t60 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6t60 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/V5VHN7_ACIBA V5VHN7_ACIBA] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The spread of antibiotic resistance within the ESKAPE group of human pathogenic bacteria poses severe challenges in the treatment of infections and maintenance of safe hospital environments. This motivates efforts to validate novel target proteins within these species that could be pursued as potential targets for antibiotic development. Genetic data suggest that the enzyme FabG, which is part of the bacterial fatty acid biosynthetic system FAS-II, is essential in several ESKAPE pathogens. FabG catalyzes the NADPH dependent reduction of 3-keto-acyl-ACP during fatty acid elongation, thus enabling lipid supply for production and maintenance of the cell envelope. Here we report on small-molecule screening on the FabG enzymes from A. baumannii and S. typhimurium to identify a set of microM inhibitors, with the most potent representative (1) demonstrating activity against six FabG-orthologues. A co-crystal structure with FabG from A. baumannii (PDB:6T65) confirms inhibitor binding at an allosteric site located in the subunit interface, as previously demonstrated for other sub-microM inhibitors of FabG from P. aeruginosa. We show that inhibitor binding distorts the oligomerization interface in the FabG tetramer and displaces crucial residues involved in the interaction with the co-substrate NADPH. These observations suggest a conserved allosteric site across the FabG family, which can be potentially targeted for interference with fatty acid biosynthesis in clinically relevant ESKAPE pathogens.

A FabG inhibitor targeting an allosteric binding site inhibits several orthologs from Gram-negative ESKAPE pathogens.,Vella P, Rudraraju RS, Lundback T, Axelsson H, Almqvist H, Vallin M, Schneider G, Schnell R Bioorg Med Chem. 2021 Jan 15;30:115898. doi: 10.1016/j.bmc.2020.115898. Epub 2020, Dec 5. PMID:33388594<ref>PMID:33388594</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6t60" style="background-color:#fffaf0;"></div>

==See Also==
*[[Beta-hydroxyacyl-acyl carrier protein dehydratase 3D structures|Beta-hydroxyacyl-acyl carrier protein dehydratase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Acinetobacter baumannii]]
[[Category: Large Structures]]
[[Category: Schneider G]]
[[Category: Schnell R]]
[[Category: Vella P]]