4cs6

Crystal structure of AadA - an aminoglycoside adenyltransferase

spinqualitylabelsall models 4cs6, resolution 2.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4cs6 is a 1 chain structure with sequence from Salmonella enterica subsp. enterica serovar Typhimurium str. LT2. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.502Å Ligands: CSS Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function S3AD_SALTY Mediates bacterial resistance to the antibiotics streptomycin and spectinomycin, does not confer resistance to kanamycin (PubMed:26527143). Binds ATP first, then antibiotic (PubMed:26527143, PubMed:29871922). Publication Abstract from PubMed Aminoglycoside resistance is commonly conferred by enzymatic modification of drugs by aminoglycoside-modifying enzymes such as aminoglycoside nucleotidyltransferases (ANTs). Here, the first crystal structure of an ANT(3)(9) adenyltransferase, AadA from Salmonella enterica, is presented. AadA catalyses the magnesium-dependent transfer of adenosine monophosphate from ATP to the two chemically dissimilar drugs streptomycin and spectinomycin. The structure was solved using selenium SAD phasing and refined to 2.5 A resolution. AadA consists of a nucleotidyltransferase domain and an alpha-helical bundle domain. AadA crystallizes as a monomer and is a monomer in solution as confirmed by small-angle X-ray scattering, in contrast to structurally similar homodimeric adenylating enzymes such as kanamycin nucleotidyltransferase. Isothermal titration calorimetry experiments show that ATP binding has to occur before binding of the aminoglycoside substrate, and structure analysis suggests that ATP binding repositions the two domains for aminoglycoside binding in the interdomain cleft. Candidate residues for ligand binding and catalysis were subjected to site-directed mutagenesis. In vivo resistance and in vitro binding assays support the role of Glu87 as the catalytic base in adenylation, while Arg192 and Lys205 are shown to be critical for ATP binding. Structure of AadA from Salmonella enterica: a monomeric aminoglycoside (3)(9) adenyltransferase.,Chen Y, Nasvall J, Wu S, Andersson DI, Selmer M Acta Crystallogr D Biol Crystallogr. 2015 Nov 1;71(Pt 11):2267-77. doi:, 10.1107/S1399004715016429. Epub 2015 Oct 31. PMID:26527143 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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