2jjg

Crystal structure of the M. tuberculosis Lysine-epsilon aminotransferase (Rv3290c) complexed to an inhibitor

spinqualitylabelsall models 2jjg, resolution 2.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2jjg is a 1 chain structure with sequence from Mycobacterium tuberculosis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.4Å Ligands: L18, PLP Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function LAT_MYCTU 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 Lysine varepsilon-aminotransferase (LAT) converts lysine to alpha-aminoadipate-delta-semialdehyde in a PLP-mediated reaction. We mutated active-site T330, N328 and E243, and structurally rationalized their properties. T330A and T330S mutants cannot bind PLP and are inactive. N328A although inactive, binds to PLP. E243A retains activity, but binds alpha-ketoglutarate in a different conformation. We had earlier identified 2-aminomethyl piperidine derivative as a LAT inhibitor. The co-crystal structure reveals that it mimics binding of C5 substrates and exhibits two binding modes. E243, that shields R422 in the apo enzyme, exhibits conformational changes to permit the binding of the inhibitor in one of the binding modes. Structure-based analysis of bound water in the active site suggests optimization strategies for synthesis of improved inhibitors. Mutational analysis of Mycobacterium tuberculosis lysine varepsilon-aminotransferase and inhibitor co-crystal structures, reveals distinct binding modes.,Tripathi SM, Agarwal A, Ramachandran R Biochem Biophys Res Commun. 2015 Jul 17-24;463(1-2):154-60. doi:, 10.1016/j.bbrc.2015.05.055. Epub 2015 May 20. PMID:26003725 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Aminotransferase 3D structures

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