Disease relevance of 3-isopropylmalic acid

• The nucleotide sequence of 3-isopropylmalate dehydrogenase gene from Bacillus subtilis [1].
• The comparison of the three-dimensional structures of thermophilic (Thermus thermophilus) and mesophilic (Escherichia coli) 3-isopropylmalate dehydrogenases (IPMDH, EC 1.1.1.85) suggested that the existence of extra ion pairs in the thermophilic enzyme found in the intersubunit region may be an important factor for thermostability [2].
• Sequence and homology model of 3-isopropylmalate dehydrogenase from the psychrotrophic bacterium Vibrio sp. I5 suggest reasons for thermal instability [3].
• RESULTS: We have determined the crystal structure of IPMDH from Thiobacillus ferrooxidans (Tf) complexed with 3-isopropylmalate (IPM) at 2.0 A resolution by the molecular replacement method [4].
• The gene of an extreme thermophile, Thermus thermophilus HB8, which codes for a leucine biosynthetic enzyme, 3-isopropylmalate (3-IPM) dehydrogenase [EC 1.1.1.85], was cloned in Escherichia coli using pBR322 as a vector [5].

High impact information on 3-isopropylmalic acid

• HICDH, the gene product, did not catalyze the conversion of 3-isopropylmalate to 2-oxoisocaproate, a leucine biosynthetic reaction, but it did recognize isocitrate, a related compound in the tricarboxylic acid cycle, as well as homoisocitrate as a substrate [6].
• The nucleotide sequence of 3-isopropylmalate dehydrogenase gene from Bacillus caldotenax [7].
• We show here that a trimethylsilylated derivative of the major methylated endogenous product of Tmt1 in yeast extracts has an identical gas chromatography retention time and an identical electron impact mass spectrum as one of the two possible monomethyl ester derivatives of (2R,3S)-3-isopropylmalate [8].
• The mutated 3-isopropylmalate dehydrogenases encoded by the leuB genes from the pseudorevertants were more thermostable than the enzyme from the temperature-sensitive strain [9].
• Screening of the saturation mutagenesis library identified two variants, Arg87Val and Arg87Thr, that were able to catalyze the oxidation of homoisocitrate, but not isocitrate or 3-isopropylmalate [10].

Biological context of 3-isopropylmalic acid

• Random mutagenesis on thermophilic 3-isopropylmalate dehydrogenases (IPMDH; EC 1.1.1.85) produced mutant enzymes which adapt to low temperatures [11].
• The deduced amino acid sequence of the product of this ORF is highly homologous to those of 3-isopropylmalate dehydrogenases from three species of mycobacteria [12].

Gene context of 3-isopropylmalic acid

• Based on sequence comparison of 3-isopropylmalate dehydrogenases from various organisms with NAD- and NADP-dependent isocitrate dehydrogenases, Ser226, Ser253 and Ile279 of 3-isopropylmalate dehydrogenase were suggested as determining the co-enzyme specificity [13].

Analytical, diagnostic and therapeutic context of 3-isopropylmalic acid

• Crystallization and preliminary X-ray analysis of 3-isopropylmalate dehydrogenase from the moderate facultative thermophile Bacillus coagulans [14].

References