3r1k | pdb_00003r1k

Crystal structure of acetyltransferase Eis from Mycobacterium tuberculosis H37Rv in complex with CoA and an acetamide moiety

spinqualitylabelsall models 3r1k, resolution 1.95Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3r1k is a 1 chain structure with sequence from "bacillus_tuberculosis"_(zopf_1883)_klein_1884 "bacillus tuberculosis" (zopf 1883) klein 1884. The February 2012 RCSB PDB Molecule of the Month feature on Aminoglycoside Antibiotics by David Goodsell is 10.2210/rcsb_pdb/mom_2012_2. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: ACM, COA Gene: eis, Rv2416c, MT2489, MTCY253.04 ("Bacillus tuberculosis" (Zopf 1883) Klein 1884) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [EIS_MYCTU] May participate in pathogenesis, possibly by enhancing survival of the bacteria in host macrophages during infection. Publication Abstract from PubMed The emergence of multidrug-resistant and extensively drug-resistant (XDR) tuberculosis (TB) is a serious global threat. Aminoglycoside antibiotics are used as a last resort to treat XDR-TB. Resistance to the aminoglycoside kanamycin is a hallmark of XDR-TB. Here, we reveal the function and structure of the mycobacterial protein Eis responsible for resistance to kanamycin in a significant fraction of kanamycin-resistant Mycobacterium tuberculosis clinical isolates. We demonstrate that Eis has an unprecedented ability to acetylate multiple amines of many aminoglycosides. Structural and mutagenesis studies of Eis indicate that its acetylation mechanism is enabled by a complex tripartite fold that includes two general control non-derepressible 5 (GCN5)-related N-acetyltransferase regions. An intricate negatively charged substrate-binding pocket of Eis is a potential target of new antitubercular drugs expected to overcome aminoglycoside resistance. Unusual regioversatility of acetyltransferase Eis, a cause of drug resistance in XDR-TB.,Chen W, Biswas T, Porter VR, Tsodikov OV, Garneau-Tsodikova S Proc Natl Acad Sci U S A. 2011 May 31. PMID:21628583 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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