Publications

• Biochemical evidence supporting the presence of the classical mevalonate pathway in the thermoacidophilic archaeon Sulfolobus solfataricus.

  Nishimura H., Azami Y., Miyagawa M., Hashimoto C., Yoshimura T., Hemmi H.

  The existence of the classical mevalonate (MVA) pathway was examined in the thermoacidophilic archaeon Sulfolobus solfataricus. The pathway is considered uncommon among archaea because the genes of the orthologues of phosphomevalonate kinase (PMK) and/or diphosphomevalonate decarboxylase (DMD) are ... >> More

  The existence of the classical mevalonate (MVA) pathway was examined in the thermoacidophilic archaeon Sulfolobus solfataricus. The pathway is considered uncommon among archaea because the genes of the orthologues of phosphomevalonate kinase (PMK) and/or diphosphomevalonate decarboxylase (DMD) are absent in the genomes of most archaea. Instead, the modified MVA pathway, which involves isopentenyl phosphate kinase (IPK), has been proposed to exist in the archaea that lack the classical pathway. However, some archaea including S. solfataricus possess the genes of the orthologues of both IPK and all enzymes of the classical pathway. Biochemical characterization using recombinant proteins showed that the orthologues of the enzymes catalyzing the late steps of the classical pathway, i.e. MVA kinase, PMK and DMD, are all active. Moreover, in vitro conversion of the intermediates in the classical and modified pathways by cell-free extract from S. solfataricus indicated that only the classical pathway likely works in the organism. << Less

  J. Biochem. 153:415-420(2013) [PubMed] [EuropePMC]

  This publication is cited by 1 other entry.

• Substrate binding order in mevalonate 5-diphosphate decarboxylase from chicken liver.

  Jabalquinto A.M., Cardemil E.

  The substrate binding order of chicken liver mevalonate 5-diphosphate decarboxylase was investigated by using competitive inhibitors of the substrates. Mevalonate and mevalonate 5-phosphate showed mixed inhibition when ATP was the varied substrate. Both analogues of ATP, adenosine 5'-O-(3-thiotrip ... >> More

  The substrate binding order of chicken liver mevalonate 5-diphosphate decarboxylase was investigated by using competitive inhibitors of the substrates. Mevalonate and mevalonate 5-phosphate showed mixed inhibition when ATP was the varied substrate. Both analogues of ATP, adenosine 5'-O-(3-thiotriphosphate) and beta-tau methylene adenosine 5'-triphosphate showed uncompetitive inhibition against mevalonate 5-diphosphate. These results are in accordance with an ordered sequential mechanism with mevalonate 5-diphosphate as the first substrate to bind to the enzyme. << Less

  Biochim Biophys Acta 996:257-259(1989) [PubMed] [EuropePMC]

• Mevalonate-5-diphosphate decarboxylase: stereochemical course of ATP-dependent phosphorylation of mevalonate 5-diphosphate.

  Iyengar R., Cardemil E., Frey P.A.

  Chicken liver mevalonate-5-diphosphate decarboxylase catalyzes the reaction of mevalonate 5-diphosphate (MVADP) with ATP to produce isopentenyl diphosphate, ADP, CO2, and inorganic phosphate. The overall reaction involves an anti elimination of the tertiary hydroxyl and carboxyl groups. To investi ... >> More

  Chicken liver mevalonate-5-diphosphate decarboxylase catalyzes the reaction of mevalonate 5-diphosphate (MVADP) with ATP to produce isopentenyl diphosphate, ADP, CO2, and inorganic phosphate. The overall reaction involves an anti elimination of the tertiary hydroxyl and carboxyl groups. To investigate the mechanism for transfer of the terminal phosphoryl group of ATP to the C-3 oxygen of MVADP, we have carried out the reaction using stereospecifically labeled (Sp)-adenosine 5'-O-(3-thio[3-17O2,18O]triphosphate) [( gamma-17O2,18O]ATP gamma S) in place of ATP. The configuration of the [17O,18O]thiophosphate produced was found to be Rp, corresponding to overall inversion of configuration at phosphorus in the thiophosphoryl group transfer step. This result is consistent with the direct transfer of the thiophosphoryl group from (Sp)-[gamma-17O2,18O]ATP gamma S to MVADP at the active site. Our result does not indicate the involvement of a covalent thiophosphoryl-enzyme on the reaction pathway. << Less

  Biochemistry 25:4693-4698(1986) [PubMed] [EuropePMC]

• Post-translational regulation of mevalonate kinase by intermediates of the cholesterol and nonsterol isoprene biosynthetic pathways.

  Hinson D.D., Chambliss K.L., Toth M.J., Tanaka R.D., Gibson K.M.

  To assess the potential for feedback inhibition by isoprene intermediates in the cholesterol and nonsterol isoprene biosynthetic pathway, we expressed human cDNAs encoding mevalonate kinase (MKase), phosphomevalonate kinase (PMKase), and mevalonate diphosphate decarboxylase (MDDase) as fusion prot ... >> More

  To assess the potential for feedback inhibition by isoprene intermediates in the cholesterol and nonsterol isoprene biosynthetic pathway, we expressed human cDNAs encoding mevalonate kinase (MKase), phosphomevalonate kinase (PMKase), and mevalonate diphosphate decarboxylase (MDDase) as fusion proteins in Escherichia coli DH5alpha, and purified these proteins by affinity chromatography. Several phosphorylated and non-phosphorylated isoprenes were analyzed as inhibitors of the enzymes using a standard spectrophotometric assay. Of the three proteins, only MKase was inhibited through competitive interaction at the ATP-binding site. The intermediates studied (and their relative inhibitory capacity) were: geranylgeranyl-diphosphate (GGPP, C20) > farnesyl-diphosphate (FPP, C15) > geranyl-diphosphate (GPP, C10) > isopentenyl-diphosphate (IPP, C5) > or = 3,3-dimethylallyl-diphosphate (DMAPP, C5) > farnesol (C15) > dolichol-phosphate (DP, C(80-100)). Mevalonate-diphosphate, geraniol, and dolichol were not inhibitors. Our data further define the spectrum of physiologic inhibitors of MKase, and provide the first evidence for feedback inhibition of MKase by a nonsterol isoprene produced by the branched pathway, dolichol-phosphate. These results provide additional evidence that MKase may occupy a central regulatory role in the control of cholesterol and nonsterol isoprene biosynthesis. << Less

  J. Lipid Res. 38:2216-2223(1997) [PubMed] [EuropePMC]

  This publication is cited by 2 other entries.

• Molecular cloning and expression of the cDNAs encoding human and yeast mevalonate pyrophosphate decarboxylase.

  Toth M.J., Huwyler L.

  The importance of lowering serum cholesterol levels for the prevention of cardiovascular disease has been well documented. Because mevalonate pyrophosphate decarboxylase is a unique enzyme in the cholesterol biosynthetic pathway it is a potential therapeutic target for the treatment of hypercholes ... >> More

  The importance of lowering serum cholesterol levels for the prevention of cardiovascular disease has been well documented. Because mevalonate pyrophosphate decarboxylase is a unique enzyme in the cholesterol biosynthetic pathway it is a potential therapeutic target for the treatment of hypercholesterolemia and other diseases. For this reason we cloned and expressed the cDNA for the human enzyme. We also cloned and expressed the yeast homolog using the human enzyme's similarity to a previously unidentified and incomplete genomic sequence. Northern blot analysis revealed a transcript of approximately 2 kilobases in a variety of human tissues. The recombinant human enzyme is a homodimer of 43-kDa subunits with a specific activity of 2.4 units/mg. Computer searches for similarity with known sequences showed that mevalonate pyrophosphate decarboxylase has little similarity to other proteins. << Less

  J. Biol. Chem. 271:7895-7898(1996) [PubMed] [EuropePMC]