Publications

• Some molecular and kinetic properties of heart malic dehydrogenase.

  WOLFE R.G., NEILANDS J.B.

  J Biol Chem 221:61-69(1956) [PubMed] [EuropePMC]

  This publication is cited by 1 other entry.

• Two malate dehydrogenases in Methanobacterium thermoautotrophicum.

  Thompson H., Tersteegen A., Thauer R.K., Hedderich R.

  Methanobacterium thermoautotrophicum (strain Marburg) was found to contain two malate dehydrogenases, which were partially purified and characterized. One was specific for NAD+ and catalyzed the dehydrogenation of malate at approximately one-third of the rate of oxalacetate reduction, and the othe ... >> More

  Methanobacterium thermoautotrophicum (strain Marburg) was found to contain two malate dehydrogenases, which were partially purified and characterized. One was specific for NAD+ and catalyzed the dehydrogenation of malate at approximately one-third of the rate of oxalacetate reduction, and the other could equally well use NAD+ and NADP+ as coenzyme and catalyzed essentially only the reduction of oxalacetate. Via the N-terminal amino acid sequences, the encoding genes were identified in the genome of M. thermoautotrophicum (strain DeltaH). Comparison of the deduced amino acid sequences revealed that the two malate dehydrogenases are phylogenetically only distantly related. The NAD+-specific malate dehydrogenase showed high sequence similarity to L-malate dehydrogenase from Methanothermus fervidus, and the NAD(P)+-using malate dehyrogenase showed high sequence similarity to L-lactate dehydrogenase from Thermotoga maritima and L-malate dehydrogenase from Bacillus subtilis. A function of the two malate dehydrogenases in NADPH:NAD+ transhydrogenation is discussed. << Less

  Arch. Microbiol. 170:38-42(1998) [PubMed] [EuropePMC]

  This publication is cited by 1 other entry.

• Beef heart malic dehydrogenases. VII. Reactivity of sulfhydryl groups and conformation of the supernatant enzyme.

  Guha A., Englard S., Listowsky I.

  J Biol Chem 243:609-615(1968) [PubMed] [EuropePMC]

  This publication is cited by 1 other entry.

• Refolding, characterization and crystal structure of (S)-malate dehydrogenase from the hyperthermophilic archaeon Aeropyrum pernix.

  Kawakami R., Sakuraba H., Goda S., Tsuge H., Ohshima T.

  Tartrate oxidation activity was found in the crude extract of an aerobic hyperthermophilic archaeon Aeropyrum pernix, and the enzyme was identified as (S)-malate dehydrogenase (MDH), which, when produced in Escherichia coli, was mainly obtained as an inactive inclusion body. The inclusion body was ... >> More

  Tartrate oxidation activity was found in the crude extract of an aerobic hyperthermophilic archaeon Aeropyrum pernix, and the enzyme was identified as (S)-malate dehydrogenase (MDH), which, when produced in Escherichia coli, was mainly obtained as an inactive inclusion body. The inclusion body was dissolved in 6 M guanidine-HCl and gradually refolded to the active enzyme through dilution of the denaturant. The purified recombinant enzyme consisted of four identical subunits with a molecular mass of about 110 kDa. NADP was preferred as a coenzyme over NAD for (S)-malate oxidation and, unlike MDHs from other sources, this enzyme readily catalyzed the oxidation of (2S,3S)-tartrate and (2S,3R)-tartrate. The tartrate oxidation activity was also observed in MDHs from the hyperthermophilic archaea Methanocaldococcus jannaschii and Archaeoglobus fulgidus, suggesting these hyperthermophilic MDHs loosely bind their substrates. The refolded A. pernix MDH was also crystallized, and the structure was determined at a resolution of 2.9 A. Its overall structure was similar to those of the M. jannaschii, Chloroflexus aurantiacus, Chlorobium vibrioforme and Cryptosporidium parvum [lactate dehydrogenase-like] MDHs with root-mean-square-deviation values between 1.4 and 2.1 A. Consistent with earlier reports, Ala at position 53 was responsible for coenzyme specificity, and the next residue, Arg, was important for NADP binding. Structural comparison revealed that the hyperthermostability of the A. pernix MDH is likely attributable to its smaller cavity volume and larger numbers of ion pairs and ion-pair networks, but the molecular strategy for thermostability may be specific for each enzyme. << Less

  Biochim. Biophys. Acta 1794:1496-1504(2009) [PubMed] [EuropePMC]

  This publication is cited by 3 other entries.

• Human phosphoglycerate dehydrogenase produces the oncometabolite D-2-hydroxyglutarate.

  Fan J., Teng X., Liu L., Mattaini K.R., Looper R.E., Vander Heiden M.G., Rabinowitz J.D.

  Human d-3-phosphoglycerate dehydrogenase (PHGDH), the first enzyme in the serine biosynthetic pathway, is genomically amplified in tumors including breast cancer and melanoma. In PHGDH-amplified cancer cells, knockdown of PHGDH is not fully rescued by exogenous serine, suggesting possible addition ... >> More

  Human d-3-phosphoglycerate dehydrogenase (PHGDH), the first enzyme in the serine biosynthetic pathway, is genomically amplified in tumors including breast cancer and melanoma. In PHGDH-amplified cancer cells, knockdown of PHGDH is not fully rescued by exogenous serine, suggesting possible additional growth-promoting roles for the enzyme. Here we show that, in addition to catalyzing oxidation of 3-phosphoglycerate, PHGDH catalyzes NADH-dependent reduction of α-ketoglutarate (AKG) to the oncometabolite d-2-hydroxyglutarate (d-2HG). Knockdown of PHGDH decreased cellular 2HG by approximately 50% in the PHGDH-amplified breast cancer cell lines MDA-MB-468 (normal concentration 93 μM) and BT-20 (normal concentration 35 μM) and overexpression of PHGDH increased cellular 2HG by over 2-fold in non-PHGDH-amplified MDA-MB-231 breast cancer cells, which normally display very low PHGDH expression. The reduced 2HG level in PHGDH knockdown cell lines can be rescued by PHGDH re-expression, but not by a catalytically inactive PHGDH mutant. The initial connection between cancer and d-2HG involved production of high levels of d-2HG by mutant isocitrate dehydrogenase. More recently, however, elevated d-2HG has been observed in breast cancer tumors without isocitrate dehydrogenase mutation. Our results suggest that PHGDH is one source of this d-2HG. << Less

  ACS Chem. Biol. 10:510-516(2015) [PubMed] [EuropePMC]

  This publication is cited by 2 other entries.

• Purification and properties of Drosophila malate dehydrogenases.

  McReynolds M.S., Kitto G.B.

  Biochim Biophys Acta 198:165-175(1970) [PubMed] [EuropePMC]

  This publication is cited by 1 other entry.