Any feedback?
Please rate this page
(literature.php)
(0/150)

BRENDA support

Literature summary for 2.7.1.185 extracted from

  • Motoyama, K.; Sobue, F.; Kawaide, H.; Yoshimura, T.; Hemmi, H.
    Conversion of mevalonate 3-kinase into 5-phosphomevalonate 3-kinase by single amino acid mutations (2019), Appl. Environ. Microbiol., 85, e00256-19 .
    View publication on PubMedView publication on EuropePMC
Search for more literature for 2.7.1.185

Cloned(Commentary)

Cloned (Comment) Organism
gene Ta1305, the pBAD-TacM plasmid series contains the genes of M3K, M3P5K, BMD, and IPK for the expression of part of modified MVA pathway II. Although the M3K, M3P5K, and IPK genes are derived from Thermoplasma acidophilum, various BMD genes have been utilized for plasmid construction. Recombinant expression of His-tagged enzyme in Escherichia coli strain BL21 Thermoplasma acidophilum

Crystallization (Commentary)

Crystallization (Comment) Organism
analysis of the substrate-complex crystal structure of TacM3K (PDB ID 4RKS) Thermoplasma acidophilum

Protein Variants

Protein Variants Comment Organism
E140A site-directed mutagenesis, inactive mutant Thermoplasma acidophilum
E140G site-directed mutagenesis, the mutation results in the conversion of mevalonate 3-kinase into 5-phosphomevalonate 3-kinase, which can synthesize 3,5-bisphosphomevalonate from 5-phosphomevalonate Thermoplasma acidophilum
E140S site-directed mutagenesis, the mutation results in the conversion of mevalonate 3-kinase into 5-phosphomevalonate 3-kinase, which can synthesize 3,5-bisphosphomevalonate from 5-phosphomevalonate Thermoplasma acidophilum
additional information substrate-interacting glutamate residue E140 of Thermoplasma acidophilum mevalonate 3-kinase is replaced by smaller amino acids, including its counterparts in diphosphomevalonate decarboxylase and phosphomevalonate decarboxylase, with the aim of altering substrate specificity. These single amino acid mutations results in the conversion of mevalonate 3-kinase into 5-phosphomevalonate 3-kinase, which can synthesize 3,5-bisphosphomevalonate from 5-phosphomevalonate. The mutants catalyzing the hitherto undiscovered reaction enables the construction of an artificial mevalonate pathway in Escherichia coli cells, as is demonstrated by the accumulation of lycopene, a red carotenoid pigment. Neither wild-type TacM3K nor any mutants show reactivity toward MVA 5-diphosphate. Alternative MVA pathway II overview. Constructed plasmids and strains, overview Thermoplasma acidophilum

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
ATP + (R)-mevalonate Thermoplasma acidophilum
-
 ADP + (R)-3-phosphomevalonate
-
 ?
ATP + (R)-mevalonate Thermoplasma acidophilum JCM 9062
-
 ADP + (R)-3-phosphomevalonate
-
 ?
ATP + (R)-mevalonate Thermoplasma acidophilum AMRC-C165
-
 ADP + (R)-3-phosphomevalonate
-
 ?
ATP + (R)-mevalonate Thermoplasma acidophilum ATCC 25905
-
 ADP + (R)-3-phosphomevalonate
-
 ?
ATP + (R)-mevalonate Thermoplasma acidophilum NBRC 15155
-
 ADP + (R)-3-phosphomevalonate
-
 ?

Organism

Organism UniProt Comment Textmining
Thermoplasma acidophilum Q9HIN1
-
-
Thermoplasma acidophilum AMRC-C165 Q9HIN1
-
-
Thermoplasma acidophilum ATCC 25905 Q9HIN1
-
-
Thermoplasma acidophilum JCM 9062 Q9HIN1
-
-
Thermoplasma acidophilum NBRC 15155 Q9HIN1
-
-

Purification (Commentary)

Purification (Comment) Organism
recombinant His-tagged enzyme from Escherichia coli strain BL21 by nickel affinity chromatography Thermoplasma acidophilum

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
ATP + (R)-mevalonate
-
 Thermoplasma acidophilum ADP + (R)-3-phosphomevalonate
-
 ?
ATP + (R)-mevalonate
-
 Thermoplasma acidophilum JCM 9062 ADP + (R)-3-phosphomevalonate
-
 ?
ATP + (R)-mevalonate
-
 Thermoplasma acidophilum AMRC-C165 ADP + (R)-3-phosphomevalonate
-
 ?
ATP + (R)-mevalonate
-
 Thermoplasma acidophilum ATCC 25905 ADP + (R)-3-phosphomevalonate
-
 ?
ATP + (R)-mevalonate
-
 Thermoplasma acidophilum NBRC 15155 ADP + (R)-3-phosphomevalonate
-
 ?
additional information substrate specificity, overview Thermoplasma acidophilum ?
-
-
additional information substrate specificity, overview Thermoplasma acidophilum JCM 9062 ?
-
-
additional information substrate specificity, overview Thermoplasma acidophilum AMRC-C165 ?
-
-
additional information substrate specificity, overview Thermoplasma acidophilum ATCC 25905 ?
-
-
additional information substrate specificity, overview Thermoplasma acidophilum NBRC 15155 ?
-
-

Synonyms

Synonyms Comment Organism
M3K
-
 Thermoplasma acidophilum
mevalonate 3-kinase
-
 Thermoplasma acidophilum
Ta1305
-
 Thermoplasma acidophilum
TacM3K
-
 Thermoplasma acidophilum

General Information

General Information Comment Organism
evolution mevalonate 3-kinase is an enzyme involved in the modified mevalonate pathway specific to limited species of thermophilic archaea Thermoplasma acidophilum
metabolism mevalonate 3-kinase plays a key role in a recently discovered modified mevalonate pathway specific to thermophilic archaea of the order Thermoplasmatales, pathway overview. In the pathway called modified MVA pathway II, mevalonate (MVA) is phosphorylated at the 3-hydroxyl group to yield 3-phosphomevalonate (MVA-3-P) by the action of mevalonate 3-kinase (M3K) rather than at the 5-hydroxyl group as in the reaction of MVK (EC 2.7.4.2). M3K is also homologous to diphosphomevalonate decarboxylase (DMD, EC 4.1.1.33). After the formation of MVA-3-P, another kinase, MVA-3-P 5-kinase (M3P5K), catalyzes its 5-phosphorylation, and a subsequent decarboxylation is catalyzed by another DMD homologue, 3,5-bisphosphomevalonate decarboxylase (BMD), to give isopentenyl phosphate (IP). IP is then phosphorylated by isopentenyl phosphate kinase (IPK) to yield isopentenyl diphosphate (IPP). The M3K enzyme is homologous to diphosphomevalonate decarboxylase, which is involved in the widely distributed classical mevalonate pathway, and to phosphomevalonate decarboxylase, which is possessed by halophilic archaea and some Chloroflexi bacteria. Neither wild-type TacM3K nor any mutants show reactivity toward MVA 5-diphosphate Thermoplasma acidophilum
additional information comparison between the substrate-complex crystal structure of TacM3K (PDB ID 4RKS) and that of Sulfolobus solfataricus DMD (SsoDMD, PDB ID 5GMD) revealing interesting differences in the structures of the active sites. The steric hindrance introduced by Glu140 seems responsible for excluding larger substrates, such as MVA 5-phosphate and MVA 5-diphosphate, from the active site of TacM3K Thermoplasma acidophilum
physiological function mevalonate 3-kinase catalyzes the ATP-dependent 3-phosphorylation of mevalonate but does not catalyze the subsequent decarboxylation as related decarboxylases do Thermoplasma acidophilum