6ahe

Crystal structure of enoyl-ACP reductase from Acinetobacter baumannii in complex with NAD and AFN-1252

spinqualitylabelsall models 6ahe, resolution 2.29Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6ahe is a 4 chain structure with sequence from Acinetobacter baumannii ATCC 19606 = CIP 70.34 = JCM 6841. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.29Å Ligands: 0WE, NAD Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function D0CAD5_ACIB2 Publication Abstract from PubMed Acinetobacter baumannii is an opportunistic Gram-negative bacterial pathogen, associated mostly with hospital-acquired infections. The emergence of drug resistance strains made it necessary to explore new pathways for the development of more effective antibiotics. Enoyl CoA reductase (FabI), a key enzyme in the fatty acid biosynthesis (FAS) pathway, has emerged as a potential target for antibacterial drug development. Earlier reports show that the lead SaFabI inhibitor AFN-1252 can inhibit FabI from other organisms including Escherichia coli and Burkholderia pseudomallei, but with differential potency. In the present work, we show that AFN-1252 is a moderate inhibitor of AbFabI with an IC50 of 216 nM. AFN-1252 stabilized AbFabI with a 4.2 degrees C increase in the melting temperature (Tm ) and, interestingly, the stabilization effect was significantly increased in presence of the cofactor NADH (Tm = 17 degrees C), suggesting the formation of a ternary complex AbFabI: AFN-1252: NADH. X-ray crystallography studies of AbFabI co-crystalized with AFN-1252 and NADH confirmed the ternary complex formation. The critical interactions of AFN-1252 with AbFabI and NADH identified from the co-crystal structure may facilitate the design and development of new drugs against A. baumannii infections by targeting the FAS pathway. Ternary complex formation of AFN-1252 with Acinetobacter baumannii FabI and NADH: Crystallographic and biochemical studies.,Rao NK, Nataraj V, Ravi M, Panchariya L, Palai K, Talapati SR, Lakshminarasimhan A, Ramachandra M, Antony T Chem Biol Drug Des. 2020 Aug;96(2):704-713. doi: 10.1111/cbdd.13686. Epub 2020, Apr 22. PMID:32227402 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Enoyl-Acyl-Carrier Protein Reductase 3D structures

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