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ADP + (R)-5-diphosphomevalonate
ATP + (R)-5-phosphomevalonate
-
-
-
r
ADPbetaS + 5-diphosphomevalonate
ATPbetaS + 5-phosphomevalonate
-
41fold slower kcat than with ADP
-
r
ATP + (R)-5-phosphomevalonate
ADP + (R)-5-diphosphomevalonate
ATP + (R)-5-phosphomevalonate
ADP + 5-diphosphomevalonate
ATP + (R)-mevalonate 5-phosphate
ADP + (R)-mevalonate 5-diphosphate
ATP + (R,S)-5-phosphomevalonate
ADP + (R,S)-5-diphosphomevalonate
ATP + 5-phosphomevalonate
ADP + 5-diphosphomevalonate
CTP + (R,S)-5-phosphomevalonate
CDP + (R,S)-5-diphosphomevalonate
GTP + (R,S)-5-phosphomevalonate
GDP + (R,S)-5-diphosphomevalonate
ITP + 5-phosphomevalonate
IDP + 5-diphosphomevalonate
-
6% of activity with ATP
-
?
TTP + (R,S)-5-phosphomevalonate
TDP + (R,S)-5-diphosphomevalonate
UTP + 5-phosphomevalonate
UDP + 5-diphosphomevalonate
-
13% of activity with ATP
-
?
additional information
?
-
ATP + (R)-5-phosphomevalonate
ADP + (R)-5-diphosphomevalonate
-
-
-
?
ATP + (R)-5-phosphomevalonate
ADP + (R)-5-diphosphomevalonate
-
-
-
?
ATP + (R)-5-phosphomevalonate
ADP + (R)-5-diphosphomevalonate
-
-
-
r
ATP + (R)-5-phosphomevalonate
ADP + (R)-5-diphosphomevalonate
-
mevalonate pathway of isopentenyl diphosphate biosynthesis
-
-
?
ATP + (R)-5-phosphomevalonate
ADP + (R)-5-diphosphomevalonate
-
mevalonate pathway of isopentenyl diphosphate biosynthesis
-
-
?
ATP + (R)-5-phosphomevalonate
ADP + (R)-5-diphosphomevalonate
-
-
-
?
ATP + (R)-5-phosphomevalonate
ADP + (R)-5-diphosphomevalonate
-
-
-
-
?
ATP + (R)-5-phosphomevalonate
ADP + (R)-5-diphosphomevalonate
-
-
-
r
ATP + (R)-5-phosphomevalonate
ADP + (R)-5-diphosphomevalonate
-
-
-
?
ATP + (R)-5-phosphomevalonate
ADP + (R)-5-diphosphomevalonate
-
-
-
-
?
ATP + (R)-5-phosphomevalonate
ADP + (R)-5-diphosphomevalonate
-
-
-
?
ATP + (R)-5-phosphomevalonate
ADP + (R)-5-diphosphomevalonate
-
mevalonate pathway of isopentenyl diphosphate biosynthesis
-
-
?
ATP + (R)-5-phosphomevalonate
ADP + (R)-5-diphosphomevalonate
-
PMK catalyzes the transfer of the gamma-phosphoryl group of ATP to (R)-5-phosphomevalonate, which results in the formation of ADP and (R)-5-diphosphomevalonate
-
-
?
ATP + (R)-5-phosphomevalonate
ADP + (R)-5-diphosphomevalonate
-
-
-
?
ATP + (R)-5-phosphomevalonate
ADP + (R)-5-diphosphomevalonate
the enzyme is involved in the classical mevalonate pathway
-
-
?
ATP + (R)-5-phosphomevalonate
ADP + (R)-5-diphosphomevalonate
-
-
-
?
ATP + (R)-5-phosphomevalonate
ADP + (R)-5-diphosphomevalonate
the enzyme is involved in the classical mevalonate pathway
-
-
?
ATP + (R)-5-phosphomevalonate
ADP + (R)-5-diphosphomevalonate
-
-
-
?
ATP + (R)-5-phosphomevalonate
ADP + (R)-5-diphosphomevalonate
-
-
-
?
ATP + (R)-5-phosphomevalonate
ADP + (R)-5-diphosphomevalonate
-
-
-
-
?
ATP + (R)-5-phosphomevalonate
ADP + (R)-5-diphosphomevalonate
-
-
-
-
ir
ATP + (R)-5-phosphomevalonate
ADP + (R)-5-diphosphomevalonate
-
active site structure and substrate binding coformation, detailed overview. Ligand binding reverses the side-chain orientations of two antiparallel lysines residues 100 and 101 with the result that Lys101 is switched into a position in which its ammonium ion is in direct contact with the beta,gamma-bridging atom of the nucleotide, where it is expected to stabilize both the ground and transition states of the reaction. The active site of PMK seems spacious enough to accommodate interconversion of the reactive and nonreactive conformers. A substantial fraction of the PMK active site is occupied by an active site water pentamer, which clusters near the charged regions of the substrate
-
-
ir
ATP + (R)-5-phosphomevalonate
ADP + (R)-5-diphosphomevalonate
-
-
-
-
r
ATP + (R)-5-phosphomevalonate
ADP + (R)-5-diphosphomevalonate
-
one of the initial steps in the biosynthesis of steroids and isoprenoids
-
-
r
ATP + (R)-5-phosphomevalonate
ADP + 5-diphosphomevalonate
-
involved in isoprenoid biosynthesis pathway
-
?
ATP + (R)-5-phosphomevalonate
ADP + 5-diphosphomevalonate
-
-
-
?
ATP + (R)-5-phosphomevalonate
ADP + 5-diphosphomevalonate
-
enzyme of mevalonate pathway
-
r
ATP + (R)-5-phosphomevalonate
ADP + 5-diphosphomevalonate
-
one of the enzymes in the biosynthetic pathway of the polyisoprenoid precursor isopentenyl diphosphate, enzyme has no regulatory function in cholesterol biosynthesis in liver
-
r
ATP + (R)-mevalonate 5-phosphate
ADP + (R)-mevalonate 5-diphosphate
-
-
-
?
ATP + (R)-mevalonate 5-phosphate
ADP + (R)-mevalonate 5-diphosphate
-
-
-
r
ATP + (R)-mevalonate 5-phosphate
ADP + (R)-mevalonate 5-diphosphate
the enzyme catalyzes a key step in isoprenoid/sterol biosynthesis
-
-
r
ATP + (R,S)-5-phosphomevalonate
ADP + (R,S)-5-diphosphomevalonate
-
-
-
-
?
ATP + (R,S)-5-phosphomevalonate
ADP + (R,S)-5-diphosphomevalonate
-
-
-
-
?
ATP + 5-phosphomevalonate
ADP + 5-diphosphomevalonate
-
-
-
?
ATP + 5-phosphomevalonate
ADP + 5-diphosphomevalonate
-
no activity with CTP and GTP
-
?
ATP + 5-phosphomevalonate
ADP + 5-diphosphomevalonate
-
-
?
ATP + 5-phosphomevalonate
ADP + 5-diphosphomevalonate
-
-
-
?
ATP + 5-phosphomevalonate
ADP + 5-diphosphomevalonate
-
-
-
?
ATP + 5-phosphomevalonate
ADP + 5-diphosphomevalonate
-
maximal activity at 10 mM ATP
-
?
ATP + 5-phosphomevalonate
ADP + 5-diphosphomevalonate
-
-
-
?
ATP + 5-phosphomevalonate
ADP + 5-diphosphomevalonate
-
-
-
?
ATP + 5-phosphomevalonate
ADP + 5-diphosphomevalonate
-
-
-
r
ATP + 5-phosphomevalonate
ADP + 5-diphosphomevalonate
-
-
-
?
ATP + 5-phosphomevalonate
ADP + 5-diphosphomevalonate
-
(3R)-phosphomevalonate
(3R)-diphosphomevalonate
r
ATP + 5-phosphomevalonate
ADP + 5-diphosphomevalonate
-
absolute specificity for ATP
-
?
ATP + 5-phosphomevalonate
ADP + 5-diphosphomevalonate
-
absolute specificity for ATP
(3R)-diphosphomevalonate
r
ATP + 5-phosphomevalonate
ADP + 5-diphosphomevalonate
-
the equilibrium constant is near unity at pH 7.5 and 30°C
(3R)-diphosphomevalonate
r
CTP + (R,S)-5-phosphomevalonate
CDP + (R,S)-5-diphosphomevalonate
-
0.4% activity
-
-
?
CTP + (R,S)-5-phosphomevalonate
CDP + (R,S)-5-diphosphomevalonate
-
0.4% activity
-
-
?
GTP + (R,S)-5-phosphomevalonate
GDP + (R,S)-5-diphosphomevalonate
-
3.6% activity
-
-
?
GTP + (R,S)-5-phosphomevalonate
GDP + (R,S)-5-diphosphomevalonate
-
3.6% activity
-
-
?
TTP + (R,S)-5-phosphomevalonate
TDP + (R,S)-5-diphosphomevalonate
-
1.6% activity
-
-
?
TTP + (R,S)-5-phosphomevalonate
TDP + (R,S)-5-diphosphomevalonate
-
1.6% activity
-
-
?
additional information
?
-
-
binding structure of AMPPNP, that interactswith both stationary and mobile regions of the PMK scaffold. The stationary region includes Ile65 and Leu66 as well as the glycine/serine-rich region, F102GLGSSGLV110, of motif II
-
-
?
additional information
?
-
-
the recombinant enzyme phosphorylates racemic vinyl, ethyl, n-propyl, n-butyl, i-butyl, 2-propenyl, allyl, ethynyl, and 1-propynyl mevalonate lactone analogues, that are phosphorylated by mevalonate kinase, EC 2.7.1.36, in a first step, overview
-
-
?
additional information
?
-
-
ATP binding structue analysis
-
-
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
ATP + (R)-5-phosphomevalonate
ADP + (R)-5-diphosphomevalonate
ATP + (R)-5-phosphomevalonate
ADP + 5-diphosphomevalonate
ATP + (R)-mevalonate 5-phosphate
ADP + (R)-mevalonate 5-diphosphate
the enzyme catalyzes a key step in isoprenoid/sterol biosynthesis
-
-
r
ATP + (R)-5-phosphomevalonate
ADP + (R)-5-diphosphomevalonate
-
-
-
r
ATP + (R)-5-phosphomevalonate
ADP + (R)-5-diphosphomevalonate
-
mevalonate pathway of isopentenyl diphosphate biosynthesis
-
-
?
ATP + (R)-5-phosphomevalonate
ADP + (R)-5-diphosphomevalonate
-
mevalonate pathway of isopentenyl diphosphate biosynthesis
-
-
?
ATP + (R)-5-phosphomevalonate
ADP + (R)-5-diphosphomevalonate
-
-
-
?
ATP + (R)-5-phosphomevalonate
ADP + (R)-5-diphosphomevalonate
-
-
-
-
?
ATP + (R)-5-phosphomevalonate
ADP + (R)-5-diphosphomevalonate
-
-
-
?
ATP + (R)-5-phosphomevalonate
ADP + (R)-5-diphosphomevalonate
-
-
-
r
ATP + (R)-5-phosphomevalonate
ADP + (R)-5-diphosphomevalonate
-
mevalonate pathway of isopentenyl diphosphate biosynthesis
-
-
?
ATP + (R)-5-phosphomevalonate
ADP + (R)-5-diphosphomevalonate
the enzyme is involved in the classical mevalonate pathway
-
-
?
ATP + (R)-5-phosphomevalonate
ADP + (R)-5-diphosphomevalonate
the enzyme is involved in the classical mevalonate pathway
-
-
?
ATP + (R)-5-phosphomevalonate
ADP + (R)-5-diphosphomevalonate
-
-
-
?
ATP + (R)-5-phosphomevalonate
ADP + (R)-5-diphosphomevalonate
-
-
-
?
ATP + (R)-5-phosphomevalonate
ADP + (R)-5-diphosphomevalonate
-
-
-
-
?
ATP + (R)-5-phosphomevalonate
ADP + (R)-5-diphosphomevalonate
-
-
-
-
ir
ATP + (R)-5-phosphomevalonate
ADP + (R)-5-diphosphomevalonate
-
one of the initial steps in the biosynthesis of steroids and isoprenoids
-
-
r
ATP + (R)-5-phosphomevalonate
ADP + 5-diphosphomevalonate
-
involved in isoprenoid biosynthesis pathway
-
?
ATP + (R)-5-phosphomevalonate
ADP + 5-diphosphomevalonate
-
-
-
?
ATP + (R)-5-phosphomevalonate
ADP + 5-diphosphomevalonate
-
enzyme of mevalonate pathway
-
r
ATP + (R)-5-phosphomevalonate
ADP + 5-diphosphomevalonate
-
one of the enzymes in the biosynthetic pathway of the polyisoprenoid precursor isopentenyl diphosphate, enzyme has no regulatory function in cholesterol biosynthesis in liver
-
r
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
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0.007 - 1.55
(R)-5-diphosphomevalonate
0.012 - 2.04
(R)-5-phosphomevalonate
0.007 - 1.55
(R)-mevalonate 5-diphosphate
0.034 - 2.04
(R)-mevalonate 5-phosphate
0.19
(R,S)-5-phosphomevalonate
-
-
0.042
5-phosphomevalonate
-
pH 7.2, 30°C
0.38
ADPbetaS
-
pH 7.0, 25°C
0.012
diphosphomevalonate
-
pH 7.0, 25°C
0.0042 - 0.35
phosphomevalonate
additional information
additional information
-
0.007
(R)-5-diphosphomevalonate
mutant K48M, 30°C, pH 7.0
0.041
(R)-5-diphosphomevalonate
wild-type, 30°C, pH 7.0
0.041
(R)-5-diphosphomevalonate
mutant R73M, 30°C, pH 7.0
0.044
(R)-5-diphosphomevalonate
mutant K69M, 30°C, pH 7.0
0.045
(R)-5-diphosphomevalonate
mutant R93M, 30°C, pH 7.0
0.057
(R)-5-diphosphomevalonate
mutant R138M, 30°C, pH 7.0
0.102
(R)-5-diphosphomevalonate
mutant R130M, 30°C, pH 7.0
0.139
(R)-5-diphosphomevalonate
mutant R141M, 30°C, pH 7.0
1.25
(R)-5-diphosphomevalonate
mutant R111M, 30°C, pH 7.0
1.55
(R)-5-diphosphomevalonate
mutant R84M, 30°C, pH 7.0
0.012
(R)-5-phosphomevalonate
-
pH 7.5, 30°C
0.034
(R)-5-phosphomevalonate
wild-type, 30°C, pH 7.0
0.047
(R)-5-phosphomevalonate
mutant R138M, 30°C, pH 7.0
0.048
(R)-5-phosphomevalonate
mutant R93M, 30°C, pH 7.0
0.1
(R)-5-phosphomevalonate
mutant R73M, 30°C, pH 7.0
0.102
(R)-5-phosphomevalonate
mutant R130M, 30°C, pH 7.0
0.11
(R)-5-phosphomevalonate
mutant K69M, 30°C, pH 7.0
0.131
(R)-5-phosphomevalonate
mutant K48M, 30°C, pH 7.0
0.225
(R)-5-phosphomevalonate
mutant R141M, 30°C, pH 7.0
0.88
(R)-5-phosphomevalonate
at pH 7.2 and 37°C
0.885
(R)-5-phosphomevalonate
at pH 7.2 and 30°C
1.71
(R)-5-phosphomevalonate
mutant R84M, 30°C, pH 7.0
2.04
(R)-5-phosphomevalonate
mutant R111M, 30°C, pH 7.0
0.007
(R)-mevalonate 5-diphosphate
pH 7.0, 30°C, recombinant mutant K48M
0.041
(R)-mevalonate 5-diphosphate
pH 7.0, 30°C, recombinant wild-type enzyme
0.041
(R)-mevalonate 5-diphosphate
pH 7.0, 30°C, recombinant wild-type enzyme
0.041
(R)-mevalonate 5-diphosphate
pH 7.0, 30°C, recombinant mutant R73M
0.044
(R)-mevalonate 5-diphosphate
pH 7.0, 30°C, recombinant mutant K69M
0.045
(R)-mevalonate 5-diphosphate
pH 7.0, 30°C, recombinant mutant R93M
0.047
(R)-mevalonate 5-diphosphate
pH 7.0, 30°C, recombinant mutant R18Q
0.057
(R)-mevalonate 5-diphosphate
pH 7.0, 30°C, recombinant mutant R138M
0.079
(R)-mevalonate 5-diphosphate
pH 7.0, 30°C, recombinant mutant K19M
0.102
(R)-mevalonate 5-diphosphate
pH 7.0, 30°C, recombinant mutant R130M
0.138
(R)-mevalonate 5-diphosphate
pH 7.0, 30°C, recombinant mutant D23N
0.139
(R)-mevalonate 5-diphosphate
pH 7.0, 30°C, recombinant mutant R141M
0.187
(R)-mevalonate 5-diphosphate
pH 7.0, 30°C, recombinant mutant K17M
1.25
(R)-mevalonate 5-diphosphate
pH 7.0, 30°C, recombinant mutant R111M
1.55
(R)-mevalonate 5-diphosphate
pH 7.0, 30°C, recombinant mutant R84M
0.034
(R)-mevalonate 5-phosphate
pH 7.0, 30°C, recombinant wild-type enzyme
0.034
(R)-mevalonate 5-phosphate
pH 7.0, 30°C, recombinant wild-type enzyme
0.047
(R)-mevalonate 5-phosphate
pH 7.0, 30°C, recombinant mutant R138M
0.048
(R)-mevalonate 5-phosphate
pH 7.0, 30°C, recombinant mutant R93M
0.1
(R)-mevalonate 5-phosphate
pH 7.0, 30°C, recombinant mutant R73M
0.102
(R)-mevalonate 5-phosphate
pH 7.0, 30°C, recombinant mutant R130M
0.11
(R)-mevalonate 5-phosphate
pH 7.0, 30°C, recombinant mutant K69M
0.116
(R)-mevalonate 5-phosphate
pH 7.0, 30°C, recombinant mutant D23N
0.123
(R)-mevalonate 5-phosphate
pH 7.0, 30°C, recombinant mutant R18Q
0.131
(R)-mevalonate 5-phosphate
pH 7.0, 30°C, recombinant mutant K48M
0.176
(R)-mevalonate 5-phosphate
pH 7.0, 30°C, recombinant mutant K17M
0.225
(R)-mevalonate 5-phosphate
pH 7.0, 30°C, recombinant mutant R141M
0.23
(R)-mevalonate 5-phosphate
pH 7.0, 30°C, recombinant mutant K19M
1.71
(R)-mevalonate 5-phosphate
pH 7.0, 30°C, recombinant mutant R84M
2.04
(R)-mevalonate 5-phosphate
pH 7.0, 30°C, recombinant mutant R111M
0.047
ADP
pH 7.0, 30°C, recombinant wild-type enzyme
0.047
ADP
pH 7.0, 30°C, recombinant wild-type enzyme
0.047
ADP
wild-type, 30°C, pH 7.0
0.06
ADP
pH 7.0, 30°C, recombinant mutant K48M
0.06
ADP
mutant K48M, 30°C, pH 7.0
0.065
ADP
pH 7.0, 30°C, recombinant mutant R18Q
0.079
ADP
pH 7.0, 30°C, recombinant mutant D23N
0.091
ADP
pH 7.0, 30°C, recombinant mutant R93M
0.091
ADP
mutant R93M, 30°C, pH 7.0
0.093
ADP
pH 7.0, 30°C, recombinant mutant R111M
0.093
ADP
mutant R111M, 30°C, pH 7.0
0.106
ADP
pH 7.0, 30°C, recombinant mutant K69M
0.106
ADP
mutant K69M, 30°C, pH 7.0
0.118
ADP
pH 7.0, 30°C, recombinant mutant R73M
0.118
ADP
mutant R73M, 30°C, pH 7.0
0.131
ADP
pH 7.0, 30°C, recombinant mutant K19M
0.164
ADP
pH 7.0, 30°C, recombinant mutant R130M
0.164
ADP
mutant R130M, 30°C, pH 7.0
0.238
ADP
pH 7.0, 30°C, recombinant mutant R84M
0.238
ADP
mutant R84M, 30°C, pH 7.0
0.286
ADP
pH 7.0, 30°C, recombinant mutant K17M
0.451
ADP
pH 7.0, 30°C, recombinant mutant R138M
0.451
ADP
mutant R138M, 30°C, pH 7.0
5.62
ADP
pH 7.0, 30°C, recombinant mutant R141M
5.62
ADP
mutant R141M, 30°C, pH 7.0
0.043
ATP
-
pH 7.5, 30°C
0.043
ATP
-
ATP in form of MgATP2-
0.0743
ATP
at pH 7.2 and 37°C
0.094
ATP
pH 7.0, 30°C, recombinant mutant R73M
0.094
ATP
mutant R73M, 30°C, pH 7.0
0.0983
ATP
at pH 7.2 and 30°C
0.101
ATP
pH 7.0, 30°C, recombinant mutant R93M
0.101
ATP
mutant R93M, 30°C, pH 7.0
0.107
ATP
pH 7.0, 30°C, recombinant wild-type enzyme
0.107
ATP
pH 7.0, 30°C, recombinant wild-type enzyme
0.107
ATP
wild-type, 30°C, pH 7.0
0.107
ATP
ATP in form of MgATP2-
0.229
ATP
pH 7.0, 30°C, recombinant mutant R130M
0.229
ATP
mutant R130M, 30°C, pH 7.0
0.236
ATP
pH 7.0, 30°C, recombinant mutant K48M
0.236
ATP
mutant K48M, 30°C, pH 7.0
0.268
ATP
pH 7.0, 30°C, recombinant mutant K69M
0.268
ATP
mutant K69M, 30°C, pH 7.0
0.303
ATP
pH 7.0, 30°C, recombinant mutant R84M
0.303
ATP
mutant R84M, 30°C, pH 7.0
0.518
ATP
pH 7.0, 30°C, recombinant mutant R138M
0.518
ATP
mutant R138M, 30°C, pH 7.0
0.536
ATP
pH 7.0, 30°C, recombinant mutant R18Q
0.536
ATP
ATP in form of MgATP2-
0.556
ATP
pH 7.0, 30°C, recombinant mutant K17M
0.556
ATP
ATP in form of MgATP2-
0.792
ATP
pH 7.0, 30°C, recombinant mutant R111M
0.792
ATP
mutant R111M, 30°C, pH 7.0
0.815
ATP
pH 7.0, 30°C, recombinant mutant D23N
0.815
ATP
ATP in form of MgATP2-
1.312
ATP
pH 7.0, 30°C, recombinant mutant K19M
1.312
ATP
ATP in form of MgATP2-
5.2
ATP
pH 7.0, 30°C, recombinant mutant R141M
5.2
ATP
mutant R141M, 30°C, pH 7.0
0.0042
phosphomevalonate
-
pH 7.0, 25°C
0.0082
phosphomevalonate
-
pH 7.5, 30°C
0.075
phosphomevalonate
-
-
0.35
phosphomevalonate
-
pH 7.5, 30°C
additional information
additional information
steady-state kinetics
-
additional information
additional information
-
steady-state kinetics
-
additional information
additional information
-
detailed kinetics, Bi Bi sequential ordered mechanism with phosphomevalonate as the first substrate and ADP the last product, the enzyme follows hyperbolic kinetics and a sequential mechanism, initial velocity and isotope exchange at equilibrium measurements, overview
-
additional information
additional information
-
kinetics of recombinant wild-type and mutant enzymes, overview
-
additional information
additional information
kinetics of recombinant wild-type and mutant enzymes, overview
-
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malfunction
PMVK is a gene involved in the pathogenesis of disseminated superficial porokeratosis (DSP), a rare keratinization disorder of the epidermis, which is characterized by keratotic lesions with an atrophic center encircled by a prominent peripheral ridge. PMVK deficiency or abnormal keratinocyte apoptosis can lead to porokeratosis. The Arg138* genetic variant (nonsense mutation) is involved in the development of DSP in both families. Using HaCaT cells as models, it is revealed that this variant disturbs subcellular localization, expression, and solubility of PMVK, apparent apoptosis in and under the cornoid lamella of PMVK-deficient lesional tissues is observed, with incomplete differentiation of keratinocytes
additional information
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the phosphorylation reaction mechanism of phosphomevalonate kinase is studied by using molecular dynamics and hybrid QM/MM methods, the crystal structure of PMK in complex with its substrate (R)-5-phosphomevalonate (PMV) and AMPPNP-Mg2+ (PDB ID 3GON) is used as the initial structure. MD simulations are performed for the wild-type kinase and five variants, K9R, K9M, K101R, K101M, and A293T, respectively
evolution
Cinnamomum camphora PMK has 3 PMK protein family motifs and 1 ATP binding site Gly-Leu-Gly-Ser-Ser-Ala-Ala, and its 3 D structure contains a catalytic pocket structure, proving CcPMK as a member of PMK gene family
evolution
phosphomethoxylate kinase (PMK) is a member of the GHMP kinase superfamily. The GbPMK protein has four conserved domains and one conserved region of the GHMP kinase family. GbPMK possesses a conserved sequence structure and sequence characteristics. PMK phylogenetic and molecular evolution analyses
evolution
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the enzyme belongs to the the GHMP kinase superfamily
metabolism
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phosphomevalonate kinase catalyzes the rate-limiting step for biosynthesis of isopentenyl diphosphate from mevalonate
metabolism
almost all eukaryotes, most of the MVA pathway-utilizing bacteria, and the archaea of the order Sulfolobales utilize mevalonate kinase (MVK), phosphomevalonate kinase (PMK), and diphosphomevalonate decarboxylase (DMD) for that purpose. The pathway that includes this set of enzymes is called the classical MVA pathway because it was discovered more than half a century ago
metabolism
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the enzyme is a representative kinase in the mevalonate pathway
metabolism
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almost all eukaryotes, most of the MVA pathway-utilizing bacteria, and the archaea of the order Sulfolobales utilize mevalonate kinase (MVK), phosphomevalonate kinase (PMK), and diphosphomevalonate decarboxylase (DMD) for that purpose. The pathway that includes this set of enzymes is called the classical MVA pathway because it was discovered more than half a century ago
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physiological function
Vitis vinifera x Vitis vinifera
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involved in terpenoid metabolism
physiological function
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involved in terpenoid metabolism
physiological function
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distinct from other GHMP kinases, PMK catalyzes the transfer of the gamma-phosphate of ATP to another negatively charged phosphate in the substrate. In addition, Mg2+ is only coordinated to the gamma-phosphoryl group of ATP in PMK, whereas it is coordinated to at least two phosphoryl groups of ATP in other GHMP kinases, structure-function analysis, detailed overview
physiological function
mevalonate 3-kinase catalyzes the ATP-dependent 3-phosphorylation of mevalonate but does not catalyze the subsequent decarboxylation as related decarboxylases do
physiological function
phosphomethoxylate kinase (PMK) is one of the core enzyme in the mevalonate pathway, one of the two pathways in plants that can synthase terpenoids. Terpenoids are main active ingredients of Ginkgo biloba
physiological function
the 5-phosphomevalonate kinase(PMK) is a key enzyme in mevalonate(MVA) pathway which reversibly catalyzes the phosphorylation of mevalonate 5-phosphate(MVAP) to form mevalonate-5-diphosphate(MVAPP) in the presence of ATP and divalent metal ion such as Mg2+. The expression level of CcPMK was different among five chemical types and different plant tissues
physiological function
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mevalonate 3-kinase catalyzes the ATP-dependent 3-phosphorylation of mevalonate but does not catalyze the subsequent decarboxylation as related decarboxylases do
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D23N
site-directed mutagenesis, the mutant shows highly reduced activity in both forward and reverse reactions compared to the wild-type enzyme
K17M
site-directed mutagenesis, the mutant shows reduced activity in both forward and reverse reactions compared to the wild-type enzyme
K19M
site-directed mutagenesis, the mutant shows highly reduced activity in both forward and reverse reactions compared to the wild-type enzyme
K22M
site-directed mutagenesis, the mutant shows a 10000fold reduced activity in both forward and reverse reactions compared to the wild-type enzyme, almost inactive mutant
K69M
mutant exhibits diminished Vmax values in both reaction directions with only slight Km perturbations
R18Q
site-directed mutagenesis, the mutant shows highly reduced activity in both forward and reverse reactions compared to the wild-type enzyme
A293T
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site-directed mutagenesis, structure comparison with the wild-type enzyme
K101M
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site-directed mutagenesis, structure comparison with the wild-type enzyme
K101R
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site-directed mutagenesis, structure comparison with the wild-type enzyme
K9M
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site-directed mutagenesis, structure comparison with the wild-type enzyme
K9R
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site-directed mutagenesis, structure comparison with the wild-type enzyme
additional information
analysis of the genetic basis of disseminated superficial porokeratosis (DSP) in two five-generation Chinese families with members diagnosed with DSP, whole-exome sequencing and genotyping. Identification of a nonsense variation c.412C > T (p.Arg138*) in the phosphomevalonate kinase gene (PMVK), which encodes a cytoplasmic enzyme catalyzing the conversion of mevalonate 5-phosphate to mevalonate 5-diphosphate in the mevalonate pathway. This genetic variant is involved in the development of DSP in both families. Using HaCaT cells as models, it is revealed that this variant disturbs subcellular localization, expression, and solubility of PMVK, apparent apoptosis in and under the cornoid lamella of PMVK-deficient lesional tissues is observed, with incomplete differentiation of keratinocytes. The R138* mutant shows reduced expression and solubility. Phenotypes, overview
K48M
site-directed mutagenesis, the mutant shows altered kinetics and reduced activity in both forward and reverse reactions compared to the wild-type enzyme
K48M
mutant exhibits diminished Vmax values in both reaction directions with only slight Km perturbations
R110M
no catalytic activity
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
R111M
site-directed mutagenesis, the mutant shows altered kinetics and reduced activity in both forward and reverse reactions compared to the wild-type enzyme
R111M
substantially inflated Km values for mevalonate 5-phosphate and mevalonate 5-diphosphate
R130M
site-directed mutagenesis, the mutant shows altered kinetics and reduced activity in both forward and reverse reactions compared to the wild-type enzyme
R130M
mutant exhibits slight changes in Vmax values in both reaction directions with slight Km perturbations
R138M
site-directed mutagenesis, the mutant shows altered kinetics and reduced activity in both forward and reverse reactions compared to the wild-type enzyme
R138M
mutant exhibits slight changes in Vmax values in both reaction directions with slight Km perturbations
R141M
site-directed mutagenesis, the mutant shows altered kinetics and reduced activity in both forward and reverse reactions compared to the wild-type enzyme
R141M
50fold increase in Km value for ATP, 120fold increase for ADP
R73M
site-directed mutagenesis, the mutant shows altered kinetics and reduced activity in both forward and reverse reactions compared to the wild-type enzyme
R73M
mutant exhibits diminished Vmax values in both reaction directions with only slight Km perturbations
R84M
site-directed mutagenesis, the mutant shows altered kinetics and reduced activity in both forward and reverse reactions compared to the wild-type enzyme
R84M
50- and 33fold increase in Km value for mevalonate 5-phosphate and mevalonate 5-diphosphate, respectively
R93M
site-directed mutagenesis, the mutant shows altered kinetics and reduced activity in both forward and reverse reactions compared to the wild-type enzyme
R93M
mutant exhibits slight changes in Vmax values in both reaction directions with slight Km perturbations
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