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Literature summary for 2.7.4.2 extracted from

  • Herdendorf, T.J.; Miziorko, H.M.
    Functional evaluation of conserved basic residues in human phosphomevalonate kinase (2007), Biochemistry, 46, 11780-11788.
    View publication on PubMedView publication on EuropePMC
Search for more literature for 2.7.4.2

Cloned(Commentary)

Cloned (Comment) Organism
gene PMVK, expression of His-tagged wild-type enzyme and mutants in Escherichia coli strain BL21(DE3) Homo sapiens

Protein Variants

Protein Variants Comment Organism
K48M site-directed mutagenesis, the mutant shows altered kinetics and reduced activity in both forward and reverse reactions compared to the wild-type enzyme Homo sapiens
K48M mutant exhibits diminished Vmax values in both reaction directions with only slight Km perturbations Homo sapiens
K69M mutant exhibits diminished Vmax values in both reaction directions with only slight Km perturbations Homo sapiens
R110M no catalytic activity Homo sapiens
R110M site-directed mutagenesis, the mutant shows altered kinetics and highly reduced activity in both forward and reverse reactions compared to the wild-type enzyme Homo sapiens
R111M site-directed mutagenesis, the mutant shows altered kinetics and reduced activity in both forward and reverse reactions compared to the wild-type enzyme Homo sapiens
R111M substantially inflated Km values for mevalonate 5-phosphate and mevalonate 5-diphosphate Homo sapiens
R130M site-directed mutagenesis, the mutant shows altered kinetics and reduced activity in both forward and reverse reactions compared to the wild-type enzyme Homo sapiens
R130M mutant exhibits slight changes in Vmax values in both reaction directions with slight Km perturbations Homo sapiens
R138M site-directed mutagenesis, the mutant shows altered kinetics and reduced activity in both forward and reverse reactions compared to the wild-type enzyme Homo sapiens
R138M mutant exhibits slight changes in Vmax values in both reaction directions with slight Km perturbations Homo sapiens
R141M site-directed mutagenesis, the mutant shows altered kinetics and reduced activity in both forward and reverse reactions compared to the wild-type enzyme Homo sapiens
R141M 50fold increase in Km value for ATP, 120fold increase for ADP Homo sapiens
R73M site-directed mutagenesis, the mutant shows altered kinetics and reduced activity in both forward and reverse reactions compared to the wild-type enzyme Homo sapiens
R73M mutant exhibits diminished Vmax values in both reaction directions with only slight Km perturbations Homo sapiens
R84M site-directed mutagenesis, the mutant shows altered kinetics and reduced activity in both forward and reverse reactions compared to the wild-type enzyme Homo sapiens
R84M 50- and 33fold increase in Km value for mevalonate 5-phosphate and mevalonate 5-diphosphate, respectively Homo sapiens
R93M site-directed mutagenesis, the mutant shows altered kinetics and reduced activity in both forward and reverse reactions compared to the wild-type enzyme Homo sapiens
R93M mutant exhibits slight changes in Vmax values in both reaction directions with slight Km perturbations Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
(R)-5-diphosphomevalonate
-
 Homo sapiens
mevalonate 5-diphosphate product inhibition, mutants R111M and R84M show decreased sensitivity compared to the wild-type enzyme Homo sapiens

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
additional information
-
 additional information kinetics of recombinant wild-type and mutant enzymes, overview Homo sapiens
0.007
-
 (R)-mevalonate 5-diphosphate pH 7.0, 30°C, recombinant mutant K48M Homo sapiens
0.007
-
 (R)-5-diphosphomevalonate mutant K48M, 30°C, pH 7.0 Homo sapiens
0.034
-
 (R)-mevalonate 5-phosphate pH 7.0, 30°C, recombinant wild-type enzyme Homo sapiens
0.034
-
 (R)-5-phosphomevalonate wild-type, 30°C, pH 7.0 Homo sapiens
0.041
-
 (R)-mevalonate 5-diphosphate pH 7.0, 30°C, recombinant wild-type enzyme Homo sapiens
0.041
-
 (R)-mevalonate 5-diphosphate pH 7.0, 30°C, recombinant mutant R73M Homo sapiens
0.041
-
 (R)-5-diphosphomevalonate wild-type, 30°C, pH 7.0 Homo sapiens
0.041
-
 (R)-5-diphosphomevalonate mutant R73M, 30°C, pH 7.0 Homo sapiens
0.044
-
 (R)-mevalonate 5-diphosphate pH 7.0, 30°C, recombinant mutant K69M Homo sapiens
0.044
-
 (R)-5-diphosphomevalonate mutant K69M, 30°C, pH 7.0 Homo sapiens
0.045
-
 (R)-mevalonate 5-diphosphate pH 7.0, 30°C, recombinant mutant R93M Homo sapiens
0.045
-
 (R)-5-diphosphomevalonate mutant R93M, 30°C, pH 7.0 Homo sapiens
0.047
-
 ADP pH 7.0, 30°C, recombinant wild-type enzyme Homo sapiens
0.047
-
 (R)-mevalonate 5-phosphate pH 7.0, 30°C, recombinant mutant R138M Homo sapiens
0.047
-
 ADP wild-type, 30°C, pH 7.0 Homo sapiens
0.047
-
 (R)-5-phosphomevalonate mutant R138M, 30°C, pH 7.0 Homo sapiens
0.048
-
 (R)-mevalonate 5-phosphate pH 7.0, 30°C, recombinant mutant R93M Homo sapiens
0.048
-
 (R)-5-phosphomevalonate mutant R93M, 30°C, pH 7.0 Homo sapiens
0.057
-
 (R)-mevalonate 5-diphosphate pH 7.0, 30°C, recombinant mutant R138M Homo sapiens
0.057
-
 (R)-5-diphosphomevalonate mutant R138M, 30°C, pH 7.0 Homo sapiens
0.06
-
 ADP pH 7.0, 30°C, recombinant mutant K48M Homo sapiens
0.06
-
 ADP mutant K48M, 30°C, pH 7.0 Homo sapiens
0.091
-
 ADP pH 7.0, 30°C, recombinant mutant R93M Homo sapiens
0.091
-
 ADP mutant R93M, 30°C, pH 7.0 Homo sapiens
0.093
-
 ADP pH 7.0, 30°C, recombinant mutant R111M Homo sapiens
0.093
-
 ADP mutant R111M, 30°C, pH 7.0 Homo sapiens
0.094
-
 ATP pH 7.0, 30°C, recombinant mutant R73M Homo sapiens
0.094
-
 ATP mutant R73M, 30°C, pH 7.0 Homo sapiens
0.1
-
 (R)-mevalonate 5-phosphate pH 7.0, 30°C, recombinant mutant R73M Homo sapiens
0.1
-
 (R)-5-phosphomevalonate mutant R73M, 30°C, pH 7.0 Homo sapiens
0.101
-
 ATP pH 7.0, 30°C, recombinant mutant R93M Homo sapiens
0.101
-
 ATP mutant R93M, 30°C, pH 7.0 Homo sapiens
0.102
-
 (R)-mevalonate 5-phosphate pH 7.0, 30°C, recombinant mutant R130M Homo sapiens
0.102
-
 (R)-mevalonate 5-diphosphate pH 7.0, 30°C, recombinant mutant R130M Homo sapiens
0.102
-
 (R)-5-phosphomevalonate mutant R130M, 30°C, pH 7.0 Homo sapiens
0.102
-
 (R)-5-diphosphomevalonate mutant R130M, 30°C, pH 7.0 Homo sapiens
0.106
-
 ADP pH 7.0, 30°C, recombinant mutant K69M Homo sapiens
0.106
-
 ADP mutant K69M, 30°C, pH 7.0 Homo sapiens
0.107
-
 ATP pH 7.0, 30°C, recombinant wild-type enzyme Homo sapiens
0.107
-
 ATP wild-type, 30°C, pH 7.0 Homo sapiens
0.11
-
 (R)-mevalonate 5-phosphate pH 7.0, 30°C, recombinant mutant K69M Homo sapiens
0.11
-
 (R)-5-phosphomevalonate mutant K69M, 30°C, pH 7.0 Homo sapiens
0.118
-
 ADP pH 7.0, 30°C, recombinant mutant R73M Homo sapiens
0.118
-
 ADP mutant R73M, 30°C, pH 7.0 Homo sapiens
0.131
-
 (R)-mevalonate 5-phosphate pH 7.0, 30°C, recombinant mutant K48M Homo sapiens
0.131
-
 (R)-5-phosphomevalonate mutant K48M, 30°C, pH 7.0 Homo sapiens
0.139
-
 (R)-mevalonate 5-diphosphate pH 7.0, 30°C, recombinant mutant R141M Homo sapiens
0.139
-
 (R)-5-diphosphomevalonate mutant R141M, 30°C, pH 7.0 Homo sapiens
0.164
-
 ADP pH 7.0, 30°C, recombinant mutant R130M Homo sapiens
0.164
-
 ADP mutant R130M, 30°C, pH 7.0 Homo sapiens
0.225
-
 (R)-mevalonate 5-phosphate pH 7.0, 30°C, recombinant mutant R141M Homo sapiens
0.225
-
 (R)-5-phosphomevalonate mutant R141M, 30°C, pH 7.0 Homo sapiens
0.229
-
 ATP pH 7.0, 30°C, recombinant mutant R130M Homo sapiens
0.229
-
 ATP mutant R130M, 30°C, pH 7.0 Homo sapiens
0.236
-
 ATP pH 7.0, 30°C, recombinant mutant K48M Homo sapiens
0.236
-
 ATP mutant K48M, 30°C, pH 7.0 Homo sapiens
0.238
-
 ADP pH 7.0, 30°C, recombinant mutant R84M Homo sapiens
0.238
-
 ADP mutant R84M, 30°C, pH 7.0 Homo sapiens
0.268
-
 ATP pH 7.0, 30°C, recombinant mutant K69M Homo sapiens
0.268
-
 ATP mutant K69M, 30°C, pH 7.0 Homo sapiens
0.303
-
 ATP pH 7.0, 30°C, recombinant mutant R84M Homo sapiens
0.303
-
 ATP mutant R84M, 30°C, pH 7.0 Homo sapiens
0.451
-
 ADP pH 7.0, 30°C, recombinant mutant R138M Homo sapiens
0.451
-
 ADP mutant R138M, 30°C, pH 7.0 Homo sapiens
0.518
-
 ATP pH 7.0, 30°C, recombinant mutant R138M Homo sapiens
0.518
-
 ATP mutant R138M, 30°C, pH 7.0 Homo sapiens
0.792
-
 ATP pH 7.0, 30°C, recombinant mutant R111M Homo sapiens
0.792
-
 ATP mutant R111M, 30°C, pH 7.0 Homo sapiens
1.25
-
 (R)-mevalonate 5-diphosphate pH 7.0, 30°C, recombinant mutant R111M Homo sapiens
1.25
-
 (R)-5-diphosphomevalonate mutant R111M, 30°C, pH 7.0 Homo sapiens
1.55
-
 (R)-mevalonate 5-diphosphate pH 7.0, 30°C, recombinant mutant R84M Homo sapiens
1.55
-
 (R)-5-diphosphomevalonate mutant R84M, 30°C, pH 7.0 Homo sapiens
1.71
-
 (R)-mevalonate 5-phosphate pH 7.0, 30°C, recombinant mutant R84M Homo sapiens
1.71
-
 (R)-5-phosphomevalonate mutant R84M, 30°C, pH 7.0 Homo sapiens
2.04
-
 (R)-mevalonate 5-phosphate pH 7.0, 30°C, recombinant mutant R111M Homo sapiens
2.04
-
 (R)-5-phosphomevalonate mutant R111M, 30°C, pH 7.0 Homo sapiens
5.2
-
 ATP pH 7.0, 30°C, recombinant mutant R141M Homo sapiens
5.2
-
 ATP mutant R141M, 30°C, pH 7.0 Homo sapiens
5.62
-
 ADP pH 7.0, 30°C, recombinant mutant R141M Homo sapiens
5.62
-
 ADP mutant R141M, 30°C, pH 7.0 Homo sapiens

Metals/Ions

Metals/Ions Comment Organism Structure
Mg2+ a cation-dependent reaction Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
ATP + (R)-5-phosphomevalonate Homo sapiens
-
 ADP + (R)-5-diphosphomevalonate
-
 r

Organism

Organism UniProt Comment Textmining
Homo sapiens
-
-
-
Homo sapiens Q15126 gene PMVK
-

Purification (Commentary)

Purification (Comment) Organism
recombinant His-tagged wild-type and mutant enzymes from Escherichia coli by nickel affinity chromatography Homo sapiens

Reaction

Reaction Comment Organism Reaction ID
ATP + (R)-5-phosphomevalonate = ADP + (R)-5-diphosphomevalonate residue R110 is important to PMK catalysis, which is also influenced by K48 and R73. R111 and R84 contribute to binding of mevalonate 5-phosphate and R141 to binding of ATP Homo sapiens
a

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
ADP + (R)-5-diphosphomevalonate
-
 Homo sapiens ATP + (R)-5-phosphomevalonate
-
 r
ATP + (R)-5-phosphomevalonate
-
 Homo sapiens ADP + (R)-5-diphosphomevalonate
-
 r
ATP + (R)-mevalonate 5-phosphate
-
 Homo sapiens ADP + (R)-mevalonate 5-diphosphate
-
 ?

Synonyms

Synonyms Comment Organism
PMK
-
 Homo sapiens

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
30
-
 assay at Homo sapiens

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7
-
 assay at Homo sapiens

Cofactor

Cofactor Comment Organism Structure
ADP
-
 Homo sapiens
ATP binding analysis by wild-type enzyme and mutants R110M and R141M using TNP-ATP, a fluorescent analogue of ATP, overview Homo sapiens

Ki Value [mM]

Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
0.018
-
 mevalonate 5-diphosphate pH 7.0, 30°C, recombinant wild-type enzyme Homo sapiens
0.018
-
 (R)-5-diphosphomevalonate wild-type, 30°C, pH 8.0 Homo sapiens
0.806
-
 mevalonate 5-diphosphate pH 7.0, 30°C, recombinant mutant R111M Homo sapiens
0.806
-
 (R)-5-diphosphomevalonate mutant R111M, 30°C, pH 8.0 Homo sapiens
1.14
-
 mevalonate 5-diphosphate pH 7.0, 30°C, recombinant mutant R84M Homo sapiens
1.14
-
 (R)-5-diphosphomevalonate mutant R84M, 30°C, pH 8.0 Homo sapiens