2vhv

Crystal structure of the D270A mutant of L-alanine dehydrogenase from Mycobacterium tuberculosis in complex with NADH.

spinqualitylabelsall models 2vhv, resolution 2.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2vhv is a 2 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 2.8Å Ligands: NAI Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function DHA_MYCTU Catalyzes the reversible reductive amination of pyruvate to L-alanine. However, since the physiological environment of M.tuberculosis has a neutral pH, it can be assumed that the enzyme catalyzes exclusively the formation of L-alanine. May play a role in cell wall synthesis as L-alanine is an important constituent of the peptidoglycan layer. 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 L-alanine dehydrogenase from Mycobacterium tuberculosis catalyzes the NADH-dependent reversible conversion of pyruvate and ammonia to L-alanine. Expression of the gene coding for this enzyme is up-regulated in the persistent phase of the organism, and alanine dehydrogenase is therefore a potential target for pathogen control by antibacterial compounds. We have determined the crystal structures of the apo- and holo-forms of the enzyme to 2.3 and 2.0 A resolution, respectively. The enzyme forms a hexamer of identical subunits, with the NAD-binding domains building up the core of the molecule and the substrate-binding domains located at the apical positions of the hexamer. Coenzyme binding stabilizes a closed conformation where the substrate-binding domains are rotated by about 16 degrees toward the dinucleotide-binding domains, compared to the open structure of the apo-enzyme. In the structure of the abortive ternary complex with NAD+ and pyruvate, the substrates are suitably positioned for hydride transfer between the nicotinamide ring and the C2 carbon atom of the substrate. The approach of the nucleophiles water and ammonia to pyruvate or the reaction intermediate iminopyruvate, respectively, is, however, only possible through conformational changes that make the substrate binding site more accessible. The crystal structures identified the conserved active-site residues His96 and Asp270 as potential acid/base catalysts in the reaction. Amino acid replacements of these residues by site-directed mutagenesis led to inactive mutants, further emphasizing their essential roles in the enzymatic reaction mechanism. Three-dimensional structures of apo- and holo-L-alanine dehydrogenase from Mycobacterium tuberculosis reveal conformational changes upon coenzyme binding.,Agren D, Stehr M, Berthold CL, Kapoor S, Oehlmann W, Singh M, Schneider G J Mol Biol. 2008 Apr 4;377(4):1161-73. Epub 2008 Feb 12. PMID:18304579 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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