2bkk

Crystal structure of Aminoglycoside Phosphotransferase APH(3')-IIIa in complex with the inhibitor AR_3a

spinqualitylabelsall models 2bkk, resolution 2.15Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2bkk is a 4 chain structure with sequence from "enterococcus_proteiformis"_thiercelin_and_jouhaud_1903 "enterococcus proteiformis" thiercelin and jouhaud 1903 and Synthetic construct sequences. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: ADP, MG Related: 1k1a, 1k1b, 1mj0, 1n0q, 1n0r, 1j7i, 1j7l, 1j7u, 1l8t, 1l8u, 2bkg Activity: Kanamycin kinase, with EC number 2.7.1.95 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [KKA3_ENTFL] Resistance to kanamycin and structurally-related aminoglycosides, including amikacin. 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 phosphotransferase (3')-IIIa (APH) is a bacterial kinase that confers antibiotic resistance to many pathogenic bacteria and shares structural homology with eukaryotic protein kinases. We report here the crystal structure of APH, trapped in an inactive conformation by a tailor-made inhibitory ankyrin repeat (AR) protein, at 2.15 A resolution. The inhibitor was selected from a combinatorial library of designed AR proteins. The AR protein binds the C-terminal lobe of APH and thereby stabilizes three alpha helices, which are necessary for substrate binding, in a significantly displaced conformation. BIAcore analysis and kinetic enzyme inhibition experiments are consistent with the proposed allosteric inhibition mechanism. In contrast to most small-molecule kinase inhibitors, the AR proteins are not restricted to active site binding, allowing for higher specificity. Inactive conformations of pharmaceutically relevant enzymes, as can be elucidated with the approach presented here, represent powerful starting points for rational drug design. Allosteric inhibition of aminoglycoside phosphotransferase by a designed ankyrin repeat protein.,Kohl A, Amstutz P, Parizek P, Binz HK, Briand C, Capitani G, Forrer P, Pluckthun A, Grutter MG Structure. 2005 Aug;13(8):1131-41. PMID:16084385 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Phosphotransferase

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