phosphomevalonate kinase | Lanosterol biosynthesis pathway | IUPHAR/MMV Guide to MALARIA PHARMACOLOGY

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phosphomevalonate kinase

Target id: 641

Nomenclature: phosphomevalonate kinase

Family: Lanosterol biosynthesis pathway

Annotation status:  image of an orange circle Annotated and awaiting review. Please contact us if you can help with reviewing.  » Email us

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 192 1p13-q23 PMVK phosphomevalonate kinase 5
Mouse - 192 3 F1; 3 Pmvk phosphomevalonate kinase
Rat - 194 2q34 Pmvk phosphomevalonate kinase
Previous and Unofficial Names
ATP:5-phosphomevalonate phosphotransferase | mevalonate-5-phosphate kinase | mevalonic acid phosphate kinase | phosphomevalonic kinase | PMK | HUMPMKI | PMKA
Database Links
BRENDA
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of human phosphomevalonate kinase
PDB Id:  3CH4
Resolution:  1.76Å
Species:  Human
References:  2
Enzyme Reaction
EC Number: 2.7.4.2 ATP + (R)-5-phosphomevalonate = ADP + (R)-5-diphosphomevalonate
Substrates and Reaction Kinetics
Substrate Sp. Property Value Units Standard property Standard value Assay description Assay conditions Comments Reference
ADP Hs Km 4.7x10-5 M pKm 4.3 recombinant wild type expressed in E coli, purified, in vitro spectrometic assay 30°C, pH 7.0 Reverse reaction, averaged over six measurements 3-4
ATP Hs Km 1.07x10-4 M pKm 4.0 recombinant wild type expressed in E coli, purified, in vitro spectrometic assay 30°C, pH 7.0 Forward reaction, figures averaged over 5 measurements 3-4
(R)-5-phosphomevalonate Hs Km 3.4x10-5 M pKm 4.5 recombinant wild type expressed in E coli, purified, in vitro spectrometic assay 30°C, pH 7.0 Forward reaction, figures averaged over 5 measurements 3-4
(R)-5-phosphomevalonate Rn Km 3.57x10-5 M pKm 4.4 in vitro assay, enzyme extracted from rat liver pH 7.4, 37ºC Concentration of substrates and reagents: 10mM ATP, 12.5 MgCl2, 150 µM mevalonate 5-phosphate. 7
(R)-5-diphosphomevalonate Hs Km 4.1x10-5 M pKm 4.4 recombinant wild type expressed in E coli, purified, in vitro spectrometic assay 30°C, pH 7.0 Reverse reaction, averaged over six measurements 3-4
ADP Hs Vmax 12 µmol/min/mg recombinant wild type expressed in E coli, purified, in vitro spectrometic assay 30°C, pH 7.0 Vmax value is for the reverse reaction, averaged over six measurements 3-4
ATP Hs Vmax 52 µmol/min/mg recombinant wild type expressed in E coli, purified, in vitro spectrometic assay 30°C, pH 7.0 Vmax value is for the forward reaction, figures averaged over 5 measurements 3-4
(R)-5-phosphomevalonate Hs Vmax 46.4 µmol/min/mg recombinant wild type expressed in E coli, purified, in vitro spectrometic assay 30°C, pH 7.0 Vmax value is for the forward reaction, averaged over 5 measurements 3-4
(R)-5-phosphomevalonate Rn Vmax 71 nmol/h/mg in vitro assay, enzyme extracted from rat liver pH 7.4, 37ºC Concentration of substrates and reagents: 10mM ATP, 12.5 MgCl2, 150 µM mevalonate 5-phosphate. 7
(R)-5-diphosphomevalonate Hs Vmax 11.3 µmol/min/mg recombinant wild type expressed in E coli, purified, in vitro spectrometic assay 30°C, pH 7.0 Vmax value is for the reverse reaction, averaged over six measurements 3-4
Cofactors
Cofactor Species Comments Reference
Mg2+ Human 2,4

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Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
(R)-5-diphosphomevalonate Hs Competitive 4.8 pKi 4
pKi 4.8 (Ki 1.8x10-5 M) [4]
Conditions: ATP concentration constant and saturating, 42-105µM mevalonate 5-phosphate
3-hydroxy-3-methyl-6-phosphohexanoic acid Rn Inhibition 3.8 pKi 6
pKi 3.8 (Ki 1.45x10-4 M) [6]
Conditions: Concentration of (R)-mevalonate: 50µM. Substrate: inhibitor ratio of 1.45.
cinnamic acid Rn Competitive 2.4 pKi 7
pKi 2.4 (Ki 3.85x10-3 M) [7]
Description: extracted from rat liver, in vitro assay
Conditions: pH 7.4, 37ºC. Concentration of substrates: 150µM mevalonate-5-phosphate, 10mM ATP, 12.5mM MgCl2
isoferulic acid Rn Competitive 2.4 pKi 7
pKi 2.4 (Ki 3.85x10-3 M) [7]
Description: extracted from rat liver, in vitro assay
Conditions: 150µM mevalonate-5-phosphate, 10mM ATP, 12.5mM MgCl2
View species-specific inhibitor tables
Tissue Distribution
Heart, liver, skeletal muscle, kidney and pancreas
Expression level:  High
Species:  Human
Technique:  Northern blot
References:  1
Brain, lung placenta
Expression level:  Low
Species:  Human
Technique:  Northern blot
References:  1

References

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1. Chambliss KL, Slaughter CA, Schreiner R, Hoffmann GF, Gibson KM. (1996) Molecular cloning of human phosphomevalonate kinase and identification of a consensus peroxisomal targeting sequence. J. Biol. Chem., 271 (29): 17330-4. [PMID:8663599]

2. Chang Q, Yan XX, Gu SY, Liu JF, Liang DC. (2008) Crystal structure of human phosphomevalonate kinase at 1.8 A resolution. Proteins, 73 (1): 254-8. [PMID:18618710]

3. Herdendorf TJ, Miziorko HM. (2006) Phosphomevalonate kinase: functional investigation of the recombinant human enzyme. Biochemistry, 45 (10): 3235-42. [PMID:16519518]

4. Herdendorf TJ, Miziorko HM. (2007) Functional evaluation of conserved basic residues in human phosphomevalonate kinase. Biochemistry, 46 (42): 11780-8. [PMID:17902708]

5. Olivier LM, Chambliss KL, Gibson KM, Krisans SK. (1999) Characterization of phosphomevalonate kinase: chromosomal localization, regulation, and subcellular targeting. J. Lipid Res., 40 (4): 672-9. [PMID:10191291]

6. Popjak G, Parker TS, Sarin V, Tropp BE, Engel R. (1978) Inhibition of 5-phosphomevalonate kinase by an isosteric analog of 5-phosphomevalonate. J. Am. Chem. Soc., 100 (25): 8014-8016.

7. Shama Bhat C, Ramasarma T. (1979) Inhibition of rat liver mevalonate pyrophosphate decarboxylase and mevalonate phosphate kinase by phenyl and phenolic compounds. Biochem. J., 181 (1): 143-51. [PMID:226078]

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