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Literature summary extracted from

  • Motoyama, K.; Unno, H.; Hattori, A.; Takaoka, T.; Ishikita, H.; Kawaide, H.; Yoshimura, T.; Hemmi, H.
    A single amino acid mutation converts (R)-5-diphosphomevalonate decarboxylase into a kinase (2017), J. Biol. Chem., 292, 2457-2469 .
    View publication on PubMedView publication on EuropePMC

Crystallization (Commentary)

EC Number Crystallization (Comment) Organism
2.7.1.185 purified enzyme in complex with (R)-5-diphosphomevalonate and adenosine 5'-O-(3-thio)triphosphate or with (R)-5-diphosphomevalonate and ADP, X-ray diffraction structure determination and analysis at 1.5-1.7 A resolution Saccharolobus solfataricus
4.1.1.33 purified enzyme in complex with (R)-5-diphosphomevalonate and adenosine 5'-O-(3-thio)triphosphate or with (R)-5-diphosphomevalonate and ADP, X-ray diffraction structure determination and analysis at 1.5-1.7 A resolution Saccharolobus solfataricus

Protein Variants

EC Number Protein Variants Comment Organism
2.7.1.185 D281A site-directed mutagenesis, the mutant only shows reduced diphosphomevalonate 3-kinase activity compared to wild-type, but is inactive in the process of phosphate elimination/decarboxylation Saccharolobus solfataricus
2.7.1.185 D281N site-directed mutagenesis, the mutant only shows reduced diphosphomevalonate 3-kinase activity compared to wild-type, but is inactive in the process of phosphate elimination/decarboxylation Saccharolobus solfataricus
2.7.1.185 D281T site-directed mutagenesis, the mutant only shows reduced diphosphomevalonate 3-kinase activity compared to wild-type, but is inactive in the process of phosphate elimination/decarboxylation Saccharolobus solfataricus
2.7.1.185 D281V site-directed mutagenesis, the mutant only shows reduced diphosphomevalonate 3-kinase activity compared to wild-type, but is inactive in the process of phosphate elimination/decarboxylation Saccharolobus solfataricus
4.1.1.33 D281N site-directed mutagenesis, the mutant only shows reduced diphosphomevalonate 3-kinase activity and phosphate elimination/decarboxylation Saccharolobus solfataricus
4.1.1.33 D281T site-directed mutagenesis, the mutant only shows reduced diphosphomevalonate 3-kinase activity compared to wild-type, but is inactive in the process of phosphate elimination/decarboxylation Saccharolobus solfataricus
4.1.1.33 D281V site-directed mutagenesis, the mutant only shows reduced diphosphomevalonate 3-kinase activity compared to wild-type, but is inactive in the process of phosphate elimination/decarboxylation Saccharolobus solfataricus
4.1.1.33 additional information the DMD activity, which yields IPP from MVA-5-PP in the presence of ATP, is observed only with the wild type and with the D281N mutant Saccharolobus solfataricus

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
2.7.1.185 ATP + (R)-mevalonate Saccharolobus solfataricus
-
 ADP + (R)-3-phosphomevalonate
-
 ?
2.7.1.185 ATP + (R)-mevalonate Saccharolobus solfataricus P2
-
 ADP + (R)-3-phosphomevalonate
-
 ?
2.7.1.185 ATP + (R)-mevalonate Saccharolobus solfataricus JCM 11322
-
 ADP + (R)-3-phosphomevalonate
-
 ?
2.7.1.185 ATP + (R)-mevalonate Saccharolobus solfataricus ATCC 35092
-
 ADP + (R)-3-phosphomevalonate
-
 ?
2.7.1.185 ATP + (R)-mevalonate Saccharolobus solfataricus DSM 1617
-
 ADP + (R)-3-phosphomevalonate
-
 ?
4.1.1.33 ATP + (R)-5-diphosphomevalonate Saccharolobus solfataricus
-
 ADP + phosphate + isopentenyl diphosphate + CO2
-
 ?
4.1.1.33 ATP + (R)-5-diphosphomevalonate Saccharolobus solfataricus P2
-
 ADP + phosphate + isopentenyl diphosphate + CO2
-
 ?
4.1.1.33 ATP + (R)-5-diphosphomevalonate Saccharolobus solfataricus JCM 11322
-
 ADP + phosphate + isopentenyl diphosphate + CO2
-
 ?
4.1.1.33 ATP + (R)-5-diphosphomevalonate Saccharolobus solfataricus ATCC 35092
-
 ADP + phosphate + isopentenyl diphosphate + CO2
-
 ?
4.1.1.33 ATP + (R)-5-diphosphomevalonate Saccharolobus solfataricus DSM 1617
-
 ADP + phosphate + isopentenyl diphosphate + CO2
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
2.7.1.185 Saccharolobus solfataricus
-
 i.e. Sulfolobus solfataricus
-
2.7.1.185 Saccharolobus solfataricus ATCC 35092
-
 i.e. Sulfolobus solfataricus
-
2.7.1.185 Saccharolobus solfataricus DSM 1617
-
 i.e. Sulfolobus solfataricus
-
2.7.1.185 Saccharolobus solfataricus JCM 11322
-
 i.e. Sulfolobus solfataricus
-
2.7.1.185 Saccharolobus solfataricus P2
-
 i.e. Sulfolobus solfataricus
-
4.1.1.33 Saccharolobus solfataricus Q97UL5 i.e. Sulfolobus solfataricus
-
4.1.1.33 Saccharolobus solfataricus ATCC 35092 Q97UL5 i.e. Sulfolobus solfataricus
-
4.1.1.33 Saccharolobus solfataricus DSM 1617 Q97UL5 i.e. Sulfolobus solfataricus
-
4.1.1.33 Saccharolobus solfataricus JCM 11322 Q97UL5 i.e. Sulfolobus solfataricus
-
4.1.1.33 Saccharolobus solfataricus P2 Q97UL5 i.e. Sulfolobus solfataricus
-

Reaction

EC Number Reaction Comment Organism Reaction ID
2.7.1.185 ATP + (R)-mevalonate = ADP + (R)-3-phosphomevalonate catalytic mechanism of this rare type of decarboxylase, the enzyme is bifunctional showing the reactions of diphosphomevalonate decarboxylase (EC 4.1.1.33) and mevalonate 3-kinase (EC 2.7.1.185), overview Saccharolobus solfataricus
a
4.1.1.33 ATP + (R)-5-diphosphomevalonate = ADP + phosphate + isopentenyl diphosphate + CO2 catalytic mechanism of this rare type of decarboxylase, the enzyme is bifunctional showing the reactions of diphosphomevalonate decarboxylase (EC 4.1.1.33) and mevalonate 3-kinase (EC 2.7.1.185), overview Saccharolobus solfataricus
a

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2.7.1.185 ATP + (R)-mevalonate
-
 Saccharolobus solfataricus ADP + (R)-3-phosphomevalonate
-
 ?
2.7.1.185 ATP + (R)-mevalonate
-
 Saccharolobus solfataricus P2 ADP + (R)-3-phosphomevalonate
-
 ?
2.7.1.185 ATP + (R)-mevalonate
-
 Saccharolobus solfataricus JCM 11322 ADP + (R)-3-phosphomevalonate
-
 ?
2.7.1.185 ATP + (R)-mevalonate
-
 Saccharolobus solfataricus ATCC 35092 ADP + (R)-3-phosphomevalonate
-
 ?
2.7.1.185 ATP + (R)-mevalonate
-
 Saccharolobus solfataricus DSM 1617 ADP + (R)-3-phosphomevalonate
-
 ?
2.7.1.185 additional information NMR analysis of the product Saccharolobus solfataricus ?
-
-
2.7.1.185 additional information NMR analysis of the product Saccharolobus solfataricus P2 ?
-
-
2.7.1.185 additional information NMR analysis of the product Saccharolobus solfataricus JCM 11322 ?
-
-
2.7.1.185 additional information NMR analysis of the product Saccharolobus solfataricus ATCC 35092 ?
-
-
2.7.1.185 additional information NMR analysis of the product Saccharolobus solfataricus DSM 1617 ?
-
-
4.1.1.33 ATP + (R)-5-diphosphomevalonate
-
 Saccharolobus solfataricus ADP + phosphate + isopentenyl diphosphate + CO2
-
 ?
4.1.1.33 ATP + (R)-5-diphosphomevalonate formation of isopentenyl diphosphate through the ATP-dependent phosphorylation of the 3-hydroxyl group of (R)-5-diphosphomevalonate followed by decarboxylation coupled with the elimination of the 3-phosphate group Saccharolobus solfataricus ADP + phosphate + isopentenyl diphosphate + CO2
-
 ?
4.1.1.33 ATP + (R)-5-diphosphomevalonate
-
 Saccharolobus solfataricus P2 ADP + phosphate + isopentenyl diphosphate + CO2
-
 ?
4.1.1.33 ATP + (R)-5-diphosphomevalonate formation of isopentenyl diphosphate through the ATP-dependent phosphorylation of the 3-hydroxyl group of (R)-5-diphosphomevalonate followed by decarboxylation coupled with the elimination of the 3-phosphate group Saccharolobus solfataricus P2 ADP + phosphate + isopentenyl diphosphate + CO2
-
 ?
4.1.1.33 ATP + (R)-5-diphosphomevalonate
-
 Saccharolobus solfataricus JCM 11322 ADP + phosphate + isopentenyl diphosphate + CO2
-
 ?
4.1.1.33 ATP + (R)-5-diphosphomevalonate formation of isopentenyl diphosphate through the ATP-dependent phosphorylation of the 3-hydroxyl group of (R)-5-diphosphomevalonate followed by decarboxylation coupled with the elimination of the 3-phosphate group Saccharolobus solfataricus JCM 11322 ADP + phosphate + isopentenyl diphosphate + CO2
-
 ?
4.1.1.33 ATP + (R)-5-diphosphomevalonate
-
 Saccharolobus solfataricus ATCC 35092 ADP + phosphate + isopentenyl diphosphate + CO2
-
 ?
4.1.1.33 ATP + (R)-5-diphosphomevalonate formation of isopentenyl diphosphate through the ATP-dependent phosphorylation of the 3-hydroxyl group of (R)-5-diphosphomevalonate followed by decarboxylation coupled with the elimination of the 3-phosphate group Saccharolobus solfataricus ATCC 35092 ADP + phosphate + isopentenyl diphosphate + CO2
-
 ?
4.1.1.33 ATP + (R)-5-diphosphomevalonate
-
 Saccharolobus solfataricus DSM 1617 ADP + phosphate + isopentenyl diphosphate + CO2
-
 ?
4.1.1.33 ATP + (R)-5-diphosphomevalonate formation of isopentenyl diphosphate through the ATP-dependent phosphorylation of the 3-hydroxyl group of (R)-5-diphosphomevalonate followed by decarboxylation coupled with the elimination of the 3-phosphate group Saccharolobus solfataricus DSM 1617 ADP + phosphate + isopentenyl diphosphate + CO2
-
 ?
4.1.1.33 additional information NMR analysis of the product Saccharolobus solfataricus ?
-
-
4.1.1.33 additional information NMR analysis of the product Saccharolobus solfataricus P2 ?
-
-
4.1.1.33 additional information NMR analysis of the product Saccharolobus solfataricus JCM 11322 ?
-
-
4.1.1.33 additional information NMR analysis of the product Saccharolobus solfataricus ATCC 35092 ?
-
-
4.1.1.33 additional information NMR analysis of the product Saccharolobus solfataricus DSM 1617 ?
-
-

Synonyms

EC Number Synonyms Comment Organism
2.7.1.185 M3K
-
 Saccharolobus solfataricus
2.7.1.185 More see also EC 4.1.1.33 Saccharolobus solfataricus
4.1.1.33 DMD
-
 Saccharolobus solfataricus
4.1.1.33 More see also EC 2.7.1.185 Saccharolobus solfataricus

General Information

EC Number General Information Comment Organism
2.7.1.185 malfunction site-directed mutagenesis on Asp281 creates mutants that only show diphosphomevalonate 3-kinase activity, demonstrating that the residue is required in the process of phosphate elimination/decarboxylation, rather than in the preceding phosphorylation step Saccharolobus solfataricus
2.7.1.185 additional information the conserved aspartate residue, Asp281, shows inability for proton abstraction. Substrate-complex structures of DMD (EC 4.1.1.33) and M3K, overview Saccharolobus solfataricus
2.7.1.185 physiological function the biosynthesis of isopentenyl diphosphate, a fundamental precursor for isoprenoids, via the mevalonate pathway is completed by diphosphomevalonate decarboxylase. This enzyme catalyzes the formation of isopentenyl diphosphate through the ATP-dependent phosphorylation of the 3-hydroxyl group of (R)-5-diphosphomevalonate followed by decarboxylation coupled with the elimination of the 3-phosphate group. Involvement of a long predicted intermediate, (R)-3-phospho-5-diphosphomevalonate, in the reaction of the enzyme Saccharolobus solfataricus
4.1.1.33 malfunction site-directed mutagenesis on Asp281 creates mutants that only show diphosphomevalonate 3-kinase activity, demonstrating that the residue is required in the process of phosphate elimination/decarboxylation, rather than in the preceding phosphorylation step Saccharolobus solfataricus
4.1.1.33 additional information the conserved aspartate residue, Asp281, shows inability for proton abstraction. Substrate-complex structures of DMD and M3K (EC 2.7.1.185), overview Saccharolobus solfataricus
4.1.1.33 physiological function the biosynthesis of isopentenyl diphosphate, a fundamental precursor for isoprenoids, via the mevalonate pathway is completed by diphosphomevalonate decarboxylase. This enzyme catalyzes the formation of isopentenyl diphosphate through the ATP-dependent phosphorylation of the 3-hydroxyl group of (R)-5-diphosphomevalonate followed by decarboxylation coupled with the elimination of the 3-phosphate group. Involvement of a long predicted intermediate, (R)-3-phospho-5-diphosphomevalonate, in the reaction of the enzyme Saccharolobus solfataricus