Mevalonate kinase

From Proteopedia

1 Function
2 Disease
3 Relevance
4 Structural highlights
5 3D structures of mevalonate kinase

Function

Mevalonate kinase (MK) is the first enzyme in the mevalonate pathway which synthesizes sterol isoprenoids like cholesterol and non-sterol isoprenoids like ubiquinone^[1]. MK catalyzes the conversion of mevalonate to 5-phosphomevalonate.

Disease

Mutations in MK resulting in MK deficiency cause hyperimmunoglobulinenemia D, a type of severe early-onset colitis, characterized by abdominal pain, diarrhea and vomiting^[2].

Relevance

Structural highlights

The 3D structure of MK complex with mevalonate shows the enzyme composed of 2 domains: The N-terminal and the C-terminal. The mevalonate binds in a deep cleft between the 2 domains forming H-bonds and hydrophobic interactions^[3]. Water molecules are shown as red spheres.

3D structures of mevalonate kinase

Updated on 16-January-2023

2r3v - hMK - human

2r42 - rMK + farnesyl thiopyrophosphate- rat
1kvk - rMK + ATP
4hac - MmMK - Methanosarcina mazei
6mde - MmMK + mevalonate
6mdf - MmMK + 5-phosphomevalonate
1kkh, 1vis - MK - Methancaldococcus jannaschii
2oi2 - MK + diphosphomevalonate - Streptococcus pneumaniae
2hfs - LmMK - Leishmania major
2hfu - LmMK + mevalonate
2x7i - LmMK - Staphylococcus aureus

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Mevalonate kinase complex with mevalonate (PDB code 2hfu).

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References

↑ Buhaescu I, Izzedine H. Mevalonate pathway: a review of clinical and therapeutical implications. Clin Biochem. 2007 Jun;40(9-10):575-84. doi: 10.1016/j.clinbiochem.2007.03.016., Epub 2007 Mar 31. PMID:17467679 doi:http://dx.doi.org/10.1016/j.clinbiochem.2007.03.016
↑ Levy M, Arion A, Berrebi D, Cuisset L, Jeanne-Pasquier C, Bader-Meunier B, Jung C. Severe early-onset colitis revealing mevalonate kinase deficiency. Pediatrics. 2013 Sep;132(3):e779-83. doi: 10.1542/peds.2012-3344. Epub 2013 Aug, 26. PMID:23979089 doi:http://dx.doi.org/10.1542/peds.2012-3344
↑ Sgraja T, Smith TK, Hunter WN. Structure, substrate recognition and reactivity of Leishmania major mevalonate kinase. BMC Struct Biol. 2007 Mar 30;7:20. PMID:17397541 doi:10.1186/1472-6807-7-20