4dta

Crystal Structure of F95M Aminoglycoside-2-Phosphotransferase Type IVa in Complex with AdenosineCrystal Structure of F95M Aminoglycoside-2-Phosphotransferase Type IVa in Complex with Adenosine

Structural highlights 4dta is a 2 chain structure with sequence from "streptococcus_casseliflavus"_vaughan_et_al._1979 "streptococcus casseliflavus" vaughan et al. 1979. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: Related: 4dt8, 4dt9, 4dtb Gene: aph(2)-Id ("Streptococcus casseliflavus" Vaughan et al. 1979) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Enzymatic phosphorylation through a family of enzymes called aminoglycoside O-phosphotransferases (APHs) is a major mechanism by which bacteria confer resistance to aminoglycoside antibiotics. Members of the APH(2) subfamily are of particular clinical interest because of their prevalence in pathogenic strains and their broad substrate spectra. APH(2) enzymes display differential preferences between ATP or GTP as the phosphate donor, with aminoglycoside 2-phosphotransferase IVa (APH(2)-IVa) being a member that utilizes both nucleotides at comparable efficiencies. We report here four crystal structures of APH(2)-IVa, two of the wild type enzyme and two of single amino acid mutants, each in complex with either adenosine or guanosine. Together, these structures afford a detailed look at the nucleoside-binding site architecture for this enzyme and reveal key elements that confer dual nucleotide specificity, including a solvent network in the interior of the nucleoside-binding pocket and the conformation of an interdomain linker loop. Steady state kinetic studies, as well as sequence and structural comparisons with members of the APH(2) subfamily and other aminoglycoside kinases, rationalize the different substrate preferences for these enzymes. Finally, despite poor overall sequence similarity and structural homology, analysis of the nucleoside-binding pocket of APH(2)-IVa shows a striking resemblance to that of eukaryotic casein kinase 2 (CK2), which also exhibits dual nucleotide specificity. These results, in complement with the multitude of existing inhibitors against CK2, can serve as a structural basis for the design of nucleotide-competitive inhibitors against clinically relevant APH enzymes. Structural Basis for Dual Nucleotide Selectivity of Aminoglycoside 2-Phosphotransferase IVa Provides Insight on Determinants of Nucleotide Specificity of Aminoglycoside Kinases.,Shi K, Berghuis AM J Biol Chem. 2012 Apr 13;287(16):13094-102. Epub 2012 Feb 24. PMID:22371504 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Phosphotransferase

spinqualitylabelsall models 4dta, resolution 2.35Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image