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Query: EC:1.1.1.37 (malate dehydrogenase)
 4,591 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mitochondrial and glyoxysomal isoenzymes of malate dehydrogenase (EC 1.1.1.27) from watermelon cotyledons and the mitochondrial isoenzyme from pig heart adsorbed reversibly to 5'-AMP-Sepharose. They were specifically eluted with low concentrations of NADH rather than by NAD. In contrast, the cytoplasmic isoenzymes showed no affinity to the matrix-bound ligand. These binding properties are discussed in terms of structural and regulatory differences of the particulate and soluble malate dehydrogenase isoenzymes. Affinity chromatography on 5'-AMP-Sepharose significantly improved the purification of the particulate malate dehydrogenase isoenzymes with respect to homogeneity, yield, and the number of purification steps. In the case of the glyoxysomal isoenzyme it was the essential procedure to obtain complete purification of the enzyme.
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PMID:Separation of malate dehydrogenase isoenzymes by affinity chromatography on 5'-AMP-Sepharose. 82 45

The structural locus for a soluble malate dehydrogenase (l-malate:NAD oxidoreductase, EC 1.1.1.37), mdh, lies about 1.2 min from aspB on the Escherichia coli chromosome in the sequence argG, aspB, mdh.
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PMID:Chromosomal location of mutations affecting the electrophoretic mobility of malate dehydrogenase in Escherichia coli K-12. 109 27

The crystal structure of malate dehydrogenase from Escherichia coli has been determined with a resulting R-factor of 0.187 for X-ray data from 8.0 to 1.87 A. Molecular replacement, using the partially refined structure of porcine mitochondrial malate dehydrogenase as a probe, provided initial phases. The structure of this prokaryotic enzyme is closely homologous with the mitochondrial enzyme but somewhat less similar to cytosolic malate dehydrogenase from eukaryotes. However, all three enzymes are dimeric and form the subunit-subunit interface through similar surface regions. A citrate ion, found in the active site, helps define the residues involved in substrate binding and catalysis. Two arginine residues, R81 and R153, interacting with the citrate are believed to confer substrate specificity. The hydroxyl of the citrate is hydrogen-bonded to a histidine, H177, and similar interactions could be assigned to a bound malate or oxaloacetate. Histidine 177 is also hydrogen-bonded to an aspartate, D150, to form a classic His.Asp pair. Studies of the active site cavity indicate that the bound citrate would occupy part of the site needed for the coenzyme. In a model building study, the cofactor, NAD, was placed into the coenzyme site which exists when the citrate was converted to malate and crystallographic water molecules removed. This hypothetical model of a ternary complex was energy minimized for comparison with the structure of the binary complex of porcine cytosolic malate dehydrogenase. Many residues involved in cofactor binding in the minimized E. coli malate dehydrogenase structure are homologous to coenzyme binding residues in cytosolic malate dehydrogenase. In the energy minimized structure of the ternary complex, the C-4 atom of NAD is in van der Waals' contact with the C-3 atom of the malate. A catalytic cycle involves hydride transfer between these two atoms.
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PMID:Crystal structure of Escherichia coli malate dehydrogenase. A complex of the apoenzyme and citrate at 1.87 A resolution. 150 30

A molecular graphics analysis of the features which prevent cytosolic malate dehydrogenase dimers from forming tetramers was evaluated by its success in predicting the synthesis of a version of the LDH framework which is a stable dimer. Surface residues responsible for malate dehydrogenases being dimers were revealed by superimposing the structures of two dimers of pig cytosolic malate dehydrogenase on one homologous tetramer of L-lactate dehydrogenase from Bacillus stearothermophilus. Four regions were identified as composing the P-axis dimer-dimer interface. Two regions of the dimer were surface loops that collided when built as a tetramer: a large loop (residues 203-207, KNOBI) and a small loop (residues 264-269, KNOBII), and these were candidates to explain the dimeric character of malate dehydrogenase. The analysis was tested by constructing a synthetic B. stearothermophilus lactate dehydrogenase (KNOBI) containing the large malate dehydrogenase loop (residues 203-207 being AYIKLQAKE, and extra four amino acids). The new construct was thermotolerant (90 degrees C) and enzymically active with kcat and KM (pyruvate) values similar to those of the wild-type enzyme. However, whereas the allosteric activator fructose 1,6-bisphosphate decreased KM 100 times for wild type, it had no influence on KNOBI. The molecular volumes of 1-120 microM concentrations of the construct were measured by time-resolved decay of tryptophan fluorescence anisotropy and by gel filtration. Both methods showed the molecular weight of wild type increased from dimer to tetramer with Kd about 20 microM dimer. KNOBI remained a dimer under these conditions.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Construction of a stable dimer of Bacillus stearothermophilus lactate dehydrogenase. 152 68

High levels of malate dehydrogenase were found in Trichuris ovis. Two molecular forms of the enzyme, of different cellular location and electrophoretic pattern, were isolated and purified. The activity of soluble malate dehydrogenase was greater than that of mitochondrial malate dehydrogenase. Both forms also displayed different electrophoretic profiles in comparison with purified extracts from goat (Capra hircus) liver. Substrate concentration directly affected enzyme activity. Host and parasite malate dehydrogenase activity were both inhibited by a series of benzimidazoles and pyrimidine-derived compounds, some of which markedly reduced parasite enzyme activity, but not host enzyme activity. Percentage inhibition by some pyrimidine derivatives was greater than that produced by benzimidazoles.
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PMID:Cellular distribution, purification and electrophoretic properties of malate dehydrogenase in Trichuris ovis and inhibition by benzimidazoles and pyrimidine derivatives. 261 25

The cardiovascular toxin allylamine (3-aminopropene) has been shown to concentrate in elastic and muscular tissues. In this study the 14C-moiety of [14C]allylamine was traced in aortas of adult Sprague-Dawley rats after intravenously injecting 30 microCi of [14C]allylamine (spec. act. = 0.4 mCi/mM). At 5, 10, 15 and 20 min after injection 33.3-29.8% of the 14C-moiety was sequestered in aortas; at 30 min 16.8% was still present. Subcellular fractionation of the postnuclear supernatant by isopycinic centrifugation in sucrose demonstrated that 5 min after administration of [14C]allylamine, the 14C-moiety displayed a modal density peak of 1.20 g/ml. Similar activities were observed up to 30 min exposure. This modal density was similar to the distribution pattern of mitochondria based on analysis of malate dehydrogenase activities. As early as 20 min post-exposure, mitochondrial malate dehydrogenase activities of aortic mitochondria decreased, while cytosolic malate dehydrogenase activities increased, suggesting mitochondrial membrane perturbation. We suggest that the subcellular site for allylamine injury to the aorta is the mitochondrion.
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PMID:Allylamine cardiovascular toxicity: VI. Subcellular distribution in rat aortas. 299 70

We cloned and characterized a mouse cytosolic malate dehydrogenase (cMDHase) (EC 1.1.1.37) gene, which is about 14 x 10(3) base-pairs long and is interrupted by eight introns. The 5' and 3' flanking regions and the exact sizes and boundaries of the exon blocks, including the transcription-initiation sites, were determined. The 5' end of the gene lacks the TATA and CAAT boxes characteristic of eukaryotic promoters, but contains G + C-rich sequences, one putative binding site for a cellular transcription factor, Sp1, and at least two major transcription-initiation sites. The sequences around the transcription-initiation sites are compatible with the formation of a number of potentially stable stem-loop structures. We compared structural organization of the mouse cMDHase gene with that of the previously characterized mouse mitochondrial MDHase (mMDHase) gene, and found that the conservation of intron positions spreads across much of the two genes. This result suggests that a common ancestral gene for the cytosolic MDHase and the mitochondrial MDHase was broken up by introns, before the divergence. We also compared the nucleotide sequence of the promoter region of the mouse cytosolic MDHase gene with that of the other three mouse genes coding for isoenzymes participating in the malate-aspartate shuttle, i.e. mitochondrial MDHase, cytosolic and mitochondrial aspartate aminotransferases (cAspATase and mAspATase). We found that highly conserved regions are present in the promoter region of the cAspATase gene.
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PMID:Structural organization of the mouse cytosolic malate dehydrogenase gene: comparison with that of the mouse mitochondrial malate dehydrogenase gene. 317 22

1. A new purification method for chicken liver mitochondrial malate dehydrogenase is described. The application of affinity chromatography through 5'AMP-Sepharose and Blue-Sepharose permits to obtain homogeneous preparations, with good yields (47%), in a short time (48 hr). 2. The 5'AMP-Sepharose chromatography reveals the presence of two malate dehydrogenase species in the mitochondrial extracts. 3. A comparative study of these forms point out the cytosolic nature of the minority form and suggests that its presence could be due to a slight interaction of the cytosolic malate dehydrogenase with mitochondrial membranes.
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PMID:Purification of malate dehydrogenase from chicken liver mitochondria. Existence of a small quantity of cytosolic isoenzyme. 319 11

A cDNA clone, named ppcMDH-1 and covering a part of the coding region for the porcine cytosolic malate dehydrogenase (cMDH) mRNA, was isolated from a porcine liver cDNA library. Subsequently, mouse cMDH cDNA clones were isolated from mouse liver and heart cDNA libraries, using the ppcMDH-1 cDNA as a probe. The longest clone, named pmcMDH-5, was sequenced and the primary structure of the mouse cMDH deduced from its cDNA sequence showed that the mouse cMDH consists of the 334-amino acid residues. When the amino acid sequence of the mouse cMDH was compared with that of the porcine cMDH, they shared a 93% homology. On the other hand, the amino acid sequences of mouse cMDH and mitochondrial MDH (mMDH) showed about 23% overall homology. Surprisingly, comparison of the amino acid sequences among the mammalian and bacterial MDHs revealed that the homology between the mouse cMDH and thermophilic bacterial MDH, as well as the homology between the mouse mMDH and Escherichia coli MDH, markedly exceeds the intraspecies sequence homology between mMDH and cMDH from mice.
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PMID:Cloning and sequence analysis of cDNAs encoding mammalian cytosolic malate dehydrogenase. Comparison of the amino acid sequences of mammalian and bacterial malate dehydrogenase. 331

The specific interaction of yeast citrate synthase with yeast mitochondrial inner membranes was characterized with respect to saturability of binding, pH optimum, effect of ionic strength, temperature response, and inhibition by oxalacetate. The binding ability of the inner membranes is inhibited by proteolysis and heat treatment, which implies that the membrane component(s) responsible for binding is a protein. A protein fraction from inner membranes when added to liposomes will bind citrate synthase. In addition, the binding of yeast fumarase, mitochondrial malate dehydrogenase, and cytosolic malate dehydrogenase to yeast inner membranes was examined. For these studies the yeast mitochondrial matrix enzymes, citrate synthase (from two types of yeast), malate dehydrogenase, and fumarase, as well as cytosolic malate dehydrogenase, were purified using rapid new techniques.
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PMID:The interaction of yeast citrate synthase with yeast mitochondrial inner membranes. 353 36


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