6ts9 | pdb_00006ts9

Crystal structure of GES-5 carbapenemase

spinqualitylabelsall models 6ts9, resolution 1.55Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6ts9 is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: BR, DMS, EDO Activity: Beta-lactamase, with EC number 3.5.2.6 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed The worldwide spread of beta-lactamases able to hydrolyze last resort carbapenems contributes to the antibiotic resistance problem and menaces the successful antimicrobial treatment of clinically relevant pathogens. Class A carbapenemases include members of the KPC and GES families. While drugs against KPC-type carbapenemases have recently been approved, for GES-type enzymes, no inhibitors have yet been introduced in therapy. Thus, GES carbapenemases represent important drug targets. Here, we present an in silico screening against the most prevalent GES carbapenemase, GES-5, using a lead-like compound library of commercially available compounds. The most promising candidates were selected for in vitro validation in biochemical assays against recombinant GES-5 leading to four derivatives active as high micromolar competitive inhibitors. For the best inhibitors, the ability to inhibit KPC-2 was also evaluated. The discovered inhibitors constitute promising starting points for hit to lead optimization. Targeting the Class A Carbapenemase GES-5 via Virtual Screening.,Klein R, Cendron L, Montanari M, Bellio P, Celenza G, Maso L, Tondi D, Brenk R Biomolecules. 2020 Feb 14;10(2). pii: biom10020304. doi: 10.3390/biom10020304. PMID:32075131 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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