4CS6
Crystal structure of AadA - an aminoglycoside adenyltransferase
Summary for 4CS6
| Entry DOI | 10.2210/pdb4cs6/pdb |
| Descriptor | AMINOGLYCOSIDE ADENYLTRANSFERASE (2 entities in total) |
| Functional Keywords | transferase, aminoglycoside adenyltransferase, ant(3'') |
| Biological source | SALMONELLA ENTERICA SUBSP. ENTERICA SEROVAR TYPHIMURIUM STR. LT2 |
| Total number of polymer chains | 1 |
| Total formula weight | 29590.99 |
| Authors | Chen, Y.,Nasvall, J.,Andersson, D.I.,Selmer, M. (deposition date: 2014-03-05, release date: 2015-03-25, Last modification date: 2024-11-06) |
| Primary citation | Chen, Y.,Nasvall, J.,Wu, S.,Andersson, D.I.,Selmer, M. Structure of Aada from Salmonella Enterica: A Monomeric Aminoglycoside (3'')(9) Adenyltransferase. Acta Crystallogr.,Sect.D, 71:2267-, 2015 Cited by PubMed Abstract: 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 Å resolution. AadA consists of a nucleotidyltransferase domain and an α-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. PubMed: 26527143DOI: 10.1107/S1399004715016429 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.502 Å) |
Structure validation
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