The high-resolution Structure of LeuB (Rv2995c) from Mycobacterium tuberculosis.
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.
Singh
Rajesh Kumar
RK
EMBL Hamburg Outstation, c/o DESY, Notkestr. 85, D-22603 Hamburg, Germany.
Kefala
Georgia
G
Janowski
Robert
R
Mueller-Dieckmann
Christoph
C
von Kries
Jens-Peter
JP
Weiss
Manfred S
MS
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
D009243:NAD; D000429:Alcohol Oxidoreductases; D050539:3-Isopropylmalate Dehydrogenase