Coenzyme Q5, methyltransferase explained

2-Methoxy-6-polyprenyl-1,4-benzoquinol methylase
Ec Number:2.1.1.201
Go Code:0043333

Coenzyme Q5, methyltransferase, more commonly known as COQ5, is an enzyme involved in the electron transport chain.[1] [2] [3] [4] COQ5 is located within the mitochondrial matrix and is a part of the biosynthesis of ubiquinone.[5]

Function

COQ5 has the role of catalyst in the C-methylation in the coenzyme Q biosynthesis,[5] on the benzoic ring of CoQ6, the biosynthetic intermediate,[6] in both in humans and yeast Saccharomyces cerevisiae.[5] COQ5 is one of the eleven polypeptides in yeast, that are essential for Q production. Moreover, it assembles with the CoQ-synthome, a multi-subunit complex. In humans, primary Q deficiency happens due to many COQ genes mutating. And diseases such as mitochondrial, cardiovascular, kidney and neurodegenerative diseases, are results of the decrease in Q biosynthesis.[5] Development of soluble COQ5 proteins can be applied to other mitochondrial proteins. Coenzyme Q10 Deficiency is associated with COQ5. Therefore, to maintain CoQ10 levels in human cells, COQ5 is required.[6] [7]

Catalytic activity

Catalyzes C-methylation and ubiquinone biosynthetic process.[8]

Mechanism

COQ5 is an S-adenosyl methionine (SAM)-dependent methyltransferase (SAM-MTase) catalyzing the C-methylation step, converting 2-methoxy-6-polyprenyl-1,4-benzoquinone (DDMQH2) to 2-methoxy-5-methyl-6-polyprenyl-1,4-benzoquinone (DMQH2) in the CoQ6 biosynthesis pathway.[9]

In the catalytic mechanism of COQ5, based on the structural analyses, as the first step, before methyl transfer, Arg201 abstracts a hydrogen from the water molecule, forming a negatively charged oxygen atom which deprotonates the C5 atom of DDMQH2. Looking at the DDMQH2 substrate and Asn202, the hydroxyl group on the C4 atom and the side chain forms a hydrogen bond which leads to the formation of the O4′ anion. The stability of the C5 anion is a result of the negative charge being delocalized on the π bond conjugation system. Tyr78 acts as a catalytic base and Tyr78, Arg201 and Asn202 are invariant in COQ5 homologues.[9] [10]

Notes and References

  1. Lee PT, Hsu AY, Ha HT, Clarke CF . A C-methyltransferase involved in both ubiquinone and menaquinone biosynthesis: isolation and identification of the Escherichia coli ubiE gene . Journal of Bacteriology . 179 . 5 . 1748–1754 . March 1997 . 9045837 . 178890 . 10.1128/jb.179.5.1748-1754.1997 .
  2. Young IG, McCann LM, Stroobant P, Gibson F . Characterization and genetic analysis of mutant strains of Escherichia coli K-12 accumulating the biquinone precursors 2-octaprenyl-6-methoxy-1,4-benzoquinone and 2-octaprenyl-3-methyl-6-methoxy-1,4-benzoquinone . Journal of Bacteriology . 105 . 3 . 769–778 . March 1971 . 4323297 . 248499 . 10.1128/jb.105.3.769-778.1971 .
  3. Dibrov E, Robinson KM, Lemire BD . The COQ5 gene encodes a yeast mitochondrial protein necessary for ubiquinone biosynthesis and the assembly of the respiratory chain . The Journal of Biological Chemistry . 272 . 14 . 9175–9181 . April 1997 . 9083048 . 10.1074/jbc.272.14.9175 . free .
  4. Barkovich RJ, Shtanko A, Shepherd JA, Lee PT, Myles DC, Tzagoloff A, Clarke CF . Characterization of the COQ5 gene from Saccharomyces cerevisiae. Evidence for a C-methyltransferase in ubiquinone biosynthesis . The Journal of Biological Chemistry . 272 . 14 . 9182–9188 . April 1997 . 9083049 . 10.1074/jbc.272.14.9182 . free .
  5. Nguyen TP, Casarin A, Desbats MA, Doimo M, Trevisson E, Santos-Ocaña C, Navas P, Clarke CF, Salviati L . 6 . Molecular characterization of the human COQ5 C-methyltransferase in coenzyme Q10 biosynthesis . Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids . 1841 . 11 . 1628–1638 . November 2014 . 25152161 . 4331671 . 10.1016/j.bbalip.2014.08.007 .
  6. Chen SW, Liu CC, Yen HC . Detection of suppressed maturation of the human COQ5 protein in the mitochondria following mitochondrial uncoupling by an antibody recognizing both precursor and mature forms of COQ5 . Mitochondrion . 13 . 2 . 143–152 . March 2013 . 23354120 . 10.1016/j.mito.2013.01.007 .
  7. Yen HC, Liu YC, Kan CC, Wei HJ, Lee SH, Wei YH, Feng YH, Chen CW, Huang CC . 6 . Disruption of the human COQ5-containing protein complex is associated with diminished coenzyme Q10 levels under two different conditions of mitochondrial energy deficiency . Biochimica et Biophysica Acta (BBA) - General Subjects . 1860 . 9 . 1864–1876 . September 2016 . 27155576 . 10.1016/j.bbagen.2016.05.005 .
  8. Web site: COQ5 Gene - Coenzyme Q5, Methyltransferase . GeneCards human gene database . Weizmann Institute of Science .
  9. Dai YN, Zhou K, Cao DD, Jiang YL, Meng F, Chi CB, Ren YM, Chen Y, Zhou CZ . 6 . Crystal structures and catalytic mechanism of the C-methyltransferase Coq5 provide insights into a key step of the yeast coenzyme Q synthesis pathway . Acta Crystallographica. Section D, Biological Crystallography . 70 . Pt 8 . 2085–2092 . August 2014 . 25084328 . 10.1107/s1399004714011559 .
  10. Huang CC, Smith CV, Glickman MS, Jacobs WR, Sacchettini JC . Crystal structures of mycolic acid cyclopropane synthases from Mycobacterium tuberculosis . The Journal of Biological Chemistry . 277 . 13 . 11559–11569 . March 2002 . 11756461 . 10.1074/jbc.m111698200 . free .

This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Coenzyme Q5, methyltransferase".

Except where otherwise indicated, Everything.Explained.Today is © Copyright 2009-2024, A B Cryer, All Rights Reserved. Cookie policy.