8qjz
From Proteopedia
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8qjz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8qjz OCA], [https://pdbe.org/8qjz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8qjz RCSB], [https://www.ebi.ac.uk/pdbsum/8qjz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8qjz 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=8qjz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8qjz OCA], [https://pdbe.org/8qjz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8qjz RCSB], [https://www.ebi.ac.uk/pdbsum/8qjz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8qjz ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| - | == | + | <div style="background-color:#fffaf0;"> |
| - | + | == Publication Abstract from PubMed == | |
| + | Here, we describe the identification of an antibiotic class acting via LpxH, a clinically unexploited target in lipopolysaccharide synthesis. The lipopolysaccharide synthesis pathway is essential in most Gram-negative bacteria and there is no analogous pathway in humans. Based on a series of phenotypic screens, we identified a hit targeting this pathway that had activity on efflux-defective strains of Escherichia coli. We recognized common structural elements between this hit and a previously published inhibitor, also with activity against efflux-deficient bacteria. With the help of X-ray structures, this information was used to design inhibitors with activity on efflux-proficient, wild-type strains. Optimization of properties such as solubility, metabolic stability and serum protein binding resulted in compounds having potent in vivo efficacy against bloodstream infections caused by the critical Gram-negative pathogens E. coli and Klebsiella pneumoniae. Other favorable properties of the series include a lack of pre-existing resistance in clinical isolates, and no loss of activity against strains expressing extended-spectrum-beta-lactamase, metallo-beta-lactamase, or carbapenemase-resistance genes. Further development of this class of antibiotics could make an important contribution to the ongoing struggle against antibiotic resistance. | ||
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| + | Antibiotic class with potent in vivo activity targeting lipopolysaccharide synthesis in Gram-negative bacteria.,Huseby DL, Cao S, Zamaratski E, Sooriyaarachchi S, Ahmad S, Bergfors T, Krasnova L, Pelss J, Ikaunieks M, Loza E, Katkevics M, Bobileva O, Cirule H, Gukalova B, Grinberga S, Backlund M, Simoff I, Leber AT, Berruga-Fernandez T, Antonov D, Konda VR, Lindstrom S, Olanders G, Brandt P, Baranczewski P, Vingsbo Lundberg C, Liepinsh E, Suna E, Jones TA, Mowbray SL, Hughes D, Karlen A Proc Natl Acad Sci U S A. 2024 Apr 9;121(15):e2317274121. doi: , 10.1073/pnas.2317274121. Epub 2024 Apr 5. PMID:38579010<ref>PMID:38579010</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 8qjz" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Current revision
Crystal structure of E. coli LpxH in complex with lipid X
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