3tyk

Crystal structure of aminoglycoside phosphotransferase APH(4)-Ia

spinqualitylabelsall models 3tyk, resolution 1.95Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3tyk is a 1 chain structure with sequence from Escherichia coli. This structure supersedes the now removed PDB entry 3ovc. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.95Å Ligands: CL, CSX, HY0, MSE Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function KHYB_ECOLX The aminoglycoside phosphotransferases achieve inactivation of their antibiotic substrates by phosphorylation. Only phosphorylates hygromycin and closely related compounds such as demethyl analogs and destomycin. Publication Abstract from PubMed The aminoglycoside phosphotransferase (APH) APH(4)-Ia is one of two enzymes responsible for bacterial resistance to the atypical aminoglycoside antibiotic hygromycin B (hygB). The crystal structure of APH(4)-Ia enzyme was solved in complex with hygB at 1.95 A resolution. The APH(4)-Ia structure adapts a general two-lobe architecture shared by other APH enzymes and eukaryotic kinases, with the active site located at the interdomain cavity. The enzyme forms an extended hydrogen bond network with hygB primarily through polar and acidic side chain groups. Individual alanine substitutions of seven residues involved in hygB binding did not have significant effect on APH(4)-Ia enzymatic activity, indicating that the binding affinity is spread across a distributed network. hygB appeared as the only substrate recognized by APH(4)-Ia among the panel of 14 aminoglycoside compounds. Analysis of the active site architecture and the interaction with the hygB molecule demonstrated several unique features supporting such restricted substrate specificity. Primarily the APH(4)-Ia substrate-binding site contains a cluster of hydrophobic residues that provides a complementary surface to the twisted structure of the substrate. Similar to APH(2) enzymes, the APH(4)-Ia is able to utilize either ATP or GTP for phosphoryl transfer. The defined structural features of APH(4)-Ia interactions with hygB and the promiscuity in regard to ATP or GTP binding could be exploited for the design of novel aminoglycoside antibiotics or inhibitors of this enzyme. Structure and function of APH(4)-Ia, a hygromycin B resistance enzyme.,Stogios PJ, Shakya T, Evdokimova E, Savchenko A, Wright GD J Biol Chem. 2011 Jan 21;286(3):1966-75. Epub 2010 Nov 17. PMID:21084294 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Phosphotransferase 3D structures

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