6rfx

Crystal structure of Eis2 from Mycobacterium abscessus

spinqualitylabelsall models 6rfx, resolution 1.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6rfx is a 6 chain structure with sequence from "mycobacterium_abcessus"_moore_and_frerichs_1953 "mycobacterium abcessus" moore and frerichs 1953. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: ACT, CIT, P4K NonStd Res: MSE Gene: D2E36_21790 ("Mycobacterium abcessus" Moore and Frerichs 1953) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Mycobacterium abscessus is an emerging human pathogen that is notorious for being one of the most drug-resistant species of Mycobacterium. It has developed numerous strategies to overcome the antibiotic stress response, limiting treatment options and leading to frequent therapeutic failure. The panel of aminoglycosides usually used in the treatment of M. abscessus pulmonary infections is restricted by chemical modification of the drugs by the N-acetyltransferase Eis2 protein (Mabs_Eis2). This enzyme acetylates the primary amine of aminoglycosides, preventing these antibiotics from binding ribosomal RNA and thereby impairing their activity. In this study, the high-resolution crystal structures of Mabs_Eis2 in its apo- and cofactor-bound forms were solved. The structural analysis of Mabs_Eis2, supported by the kinetic characterization of the enzyme, highlights the large substrate specificity of the enzyme. Furthermore, in silico docking and biochemical approaches attest that Mabs_Eis2 modifies clinically relevant drugs such as kanamycin and amikacin, with a better efficacy for the latter. In line with previous biochemical and in vivo studies, our work suggests that Mabs_Eis2 represents an attractive pharmacological target to be further explored. The high-resolution crystal structures presented here may pave the way to the design of Eis2-specific inhibitors with the potential to counteract the intrinsic resistance levels of M. abscessus to an important class of clinically important antibiotics. Crystal structure of the aminoglycosides N-acetyltransferase Eis2 from Mycobacterium abscessus.,Ung KL, Alsarraf HMAB, Olieric V, Kremer L, Blaise M FEBS J. 2019 Jun 29. doi: 10.1111/febs.14975. PMID:31254444 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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