3i0q | pdb_00003i0q

Crystal Structure of the AMP-bound complex of Spectinomycin Phosphotransferase, APH(9)-Ia

spinqualitylabelsall models 3i0q, resolution 2.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3i0q is a 1 chain structure with sequence from Legionella pneumophila. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: AMP, NI Related: 3i0o, 3i1a Gene: aph, aph9 (Legionella pneumophila) Resources: FirstGlance, OCA, RCSB, PDBsum Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed Aminoglycoside phosphotransferases (APHs) constitute a diverse group of enzymes that are often the underlying cause of aminoglycoside resistance in the clinical setting. Several APHs have been extensively characterized, including the elucidation of the three-dimensional structure of two APH(3') isozymes and an APH(2) enzyme. Although many APHs are plasmid-encoded and are capable of inactivating numerous 2-deoxystreptmaine aminoglycosides with multiple regiospecificity, APH(9)-Ia, isolated from Legionella pneumophila, is an unusual enzyme among the APH family for its chromosomal origin and its specificity for a single non-2-deoxystreptamine aminoglycoside substrate, spectinomycin. We describe here the crystal structures of APH(9)-Ia in its apo form, its binary complex with the nucleotide, AMP, and its ternary complex bound with ADP and spectinomycin. The structures reveal that APH(9)-Ia adopts the bilobal protein kinase-fold, analogous to the APH(3') and APH(2) enzymes. However, APH(9)-Ia differs significantly from the other two types of APH enzymes in its substrate binding area and that it undergoes a conformation change upon ligand binding. Moreover, kinetic assay experiments indicate that APH(9)-Ia has stringent substrate specificity as it is unable to phosphorylate substrates of choline kinase or methylthioribose kinase despite high structural resemblance. The crystal structures of APH(9)-Ia demonstrate and expand our understanding of the diversity of the APH family, which in turn will facilitate the development of new antibiotics and inhibitors. Structure of the antibiotic resistance factor spectinomycin phosphotransferase from Legionella pneumophila.,Fong DH, Lemke CT, Hwang J, Xiong B, Berghuis AM J Biol Chem. 2010 Mar 26;285(13):9545-55. Epub 2010 Jan 19. PMID:20089863 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Phosphotransferase

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