Abstract
Malate dehydrogenase (MDH), a carbohydrate and energy metabolism enzyme in eukaryotes, catalyzes the interconversion of malate to oxaloacetate (OAA) in conjunction with that of nicotinamide adenine dinucleotide (NAD+) to NADH. Three isozymes of MDH have been reported in Saccharomyces cerevisiae: MDH1, MDH2 and MDH3. MDH1 is a mitochondrial enzyme and a member of the tricarboxylic acid cycle, whereas MDH2 is a cytosolic enzyme that functions in the glyoxylate cycle. MDH3 is a glyoxysomal enzyme that is involved in the reoxidation of NADH, which is produced during fatty-acid β-oxidation. The affinity of MDH3 for OAA is lower than those of MDH1 and MDH2. Here, the crystal structures of yeast apo MDH3, the MDH3-NAD+ complex and the MDH3-NAD+-OAA ternary complex were determined. The structure of the ternary complex suggests that the active-site loop is in the open conformation, differing from the closed conformations in mitochondrial and cytosolic malate dehydrogenases.
Keywords:
MDH3; Saccharomyces cerevisiae; X-ray crystallography; fatty-acid β-oxidation; glyoxysome; malate dehydrogenase.
MeSH terms
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Amino Acid Sequence
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Apoenzymes / chemistry
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Apoenzymes / genetics
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Apoenzymes / metabolism
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Catalytic Domain
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Cloning, Molecular
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Crystallography, X-Ray
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Escherichia coli / genetics
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Escherichia coli / metabolism
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Gene Expression
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Genetic Vectors / chemistry
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Genetic Vectors / metabolism
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Glyoxysomes / chemistry
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Glyoxysomes / enzymology
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Isoenzymes / chemistry
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Isoenzymes / genetics
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Isoenzymes / metabolism
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Malate Dehydrogenase / chemistry*
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Malate Dehydrogenase / genetics
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Malate Dehydrogenase / metabolism
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Malates / chemistry*
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Malates / metabolism
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Models, Molecular
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NAD / chemistry*
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NAD / metabolism
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Oxaloacetic Acid / chemistry*
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Oxaloacetic Acid / metabolism
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Protein Binding
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Protein Conformation, alpha-Helical
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Protein Conformation, beta-Strand
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Protein Interaction Domains and Motifs
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Protein Multimerization
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Recombinant Proteins / chemistry
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
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Saccharomyces cerevisiae / chemistry*
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Saccharomyces cerevisiae / enzymology
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Saccharomyces cerevisiae Proteins / chemistry*
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Saccharomyces cerevisiae Proteins / genetics
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Saccharomyces cerevisiae Proteins / metabolism
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Sequence Alignment
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Sequence Homology, Amino Acid
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Substrate Specificity
Substances
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Apoenzymes
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Isoenzymes
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Malates
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Recombinant Proteins
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Saccharomyces cerevisiae Proteins
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NAD
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Oxaloacetic Acid
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malic acid
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Malate Dehydrogenase