title: The high-resolution Structure of LeuB (Rv2995c) from Mycobacterium tuberculosis.
abstract: The crystal structure of the enzyme 3-isopropylmalate dehydrogenase (IPMDH) from Mycobacterium tuberculosis (LeuB, Mtb-IPMDH, Rv2995c) without substrate or co-factor was determined at 1.65 A resolution, which is the highest resolution reported for an IPMDH to date. The crystals contain two functional dimers in the asymmetric unit in an arrangement close to a tetramer of D2 symmetry. Despite the absence of a substrate or inhibitor bound to the protein, the structure of the monomer resembles the previously observed closed form of the enzyme more closely than the open form. A comparison with the substrate complex of IPMDH from Thiobacillus ferrooxidans and the co-factor complex of the Thermus thermophilus enzyme revealed a close relationship of the active-site architecture between the various bacterial enzymes. The inhibitor O-isobutenyl oxalylhydroxamate was found to bind to the active site of IPMDH in a mode similar to the substrate isopropylmalate.
authors.affiliation: EMBL Hamburg Outstation, c/o DESY, Notkestr. 85, D-22603 Hamburg, Germany.
authors.forename: Rajesh Kumar
authors.initials: RK
authors.lastname: Singh
authors.forename: Georgia
authors.initials: G
authors.lastname: Kefala
authors.forename: Robert
authors.initials: R
authors.lastname: Janowski
authors.forename: Christoph
authors.initials: C
authors.lastname: Mueller-Dieckmann
authors.forename: Jens-Peter
authors.initials: JP
authors.lastname: von Kries
authors.forename: Manfred S
authors.initials: MS
authors.lastname: Weiss
mesh_terms: D050539:3-Isopropylmalate Dehydrogenase; D000429:Alcohol Oxidoreductases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D001665:Binding Sites; D002384:Catalysis; D018360:Crystallography, X-Ray; D006860:Hydrogen Bonding; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009154:Mutation / Q000235:genetics; D009169:Mycobacterium tuberculosis / Q000201:enzymology* / Q000235:genetics; D009243:NAD / Q000737:chemistry / Q000378:metabolism; D020836:Protein Structure, Quaternary; D016415:Sequence Alignment; D055672:Static Electricity
chemical_list: D009243:NAD; D000429:Alcohol Oxidoreductases; D050539:3-Isopropylmalate Dehydrogenase