Coenzyme Q5, methyltransferase

Coenzyme Q5, methyltransferase, more commonly known as COQ5, is an enzyme involved in the electron transport chain.[5][6][7][8] COQ5 is located within the mitochondrial matrix and is a part of the biosynthesis of ubiquinone.[9]

COQ5
Identifiers
AliasesCOQ5, coenzyme Q5, methyltransferase, COQ10D9
External IDsOMIM: 616359; MGI: 1098643; HomoloGene: 6559; GeneCards: COQ5; OMA:COQ5 - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_032314

NM_026504

RefSeq (protein)

NP_115690

NP_080780

Location (UCSC)Chr 12: 120.5 – 120.53 MbChr 5: 115.42 – 115.44 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse
2-Methoxy-6-polyprenyl-1,4-benzoquinol methylase
Identifiers
EC no.2.1.1.201
Databases
IntEnzIntEnz view
BRENDABRENDA entry
ExPASyNiceZyme view
KEGGKEGG entry
MetaCycmetabolic pathway
PRIAMprofile
PDB structuresRCSB PDB PDBe PDBsum
Gene OntologyAmiGO / QuickGO
Search
PMCarticles
PubMedarticles
NCBIproteins

Function

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COQ5 has the role of catalyst in the C-methylation in the coenzyme Q biosynthesis,[9] on the benzoic ring of CoQ6, the biosynthetic intermediate,[10] in both in humans and yeast Saccharomyces cerevisiae.[9] 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.[9] 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.[10][11]

Catalytic activity

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Catalyzes C-methylation and ubiquinone biosynthetic process.[12]

Mechanism

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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.[13]

 

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.[13][14]

 

References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000110871Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000041733Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Lee PT, Hsu AY, Ha HT, Clarke CF (March 1997). "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. doi:10.1128/jb.179.5.1748-1754.1997. PMC 178890. PMID 9045837.
  6. ^ Young IG, McCann LM, Stroobant P, Gibson F (March 1971). "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. doi:10.1128/jb.105.3.769-778.1971. PMC 248499. PMID 4323297.
  7. ^ Dibrov E, Robinson KM, Lemire BD (April 1997). "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. doi:10.1074/jbc.272.14.9175. PMID 9083048.
  8. ^ Barkovich RJ, Shtanko A, Shepherd JA, Lee PT, Myles DC, Tzagoloff A, Clarke CF (April 1997). "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. doi:10.1074/jbc.272.14.9182. PMID 9083049.
  9. ^ a b c d Nguyen TP, Casarin A, Desbats MA, Doimo M, Trevisson E, Santos-Ocaña C, et al. (November 2014). "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. doi:10.1016/j.bbalip.2014.08.007. PMC 4331671. PMID 25152161.
  10. ^ a b Chen SW, Liu CC, Yen HC (March 2013). "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. doi:10.1016/j.mito.2013.01.007. PMID 23354120.
  11. ^ Yen HC, Liu YC, Kan CC, Wei HJ, Lee SH, Wei YH, et al. (September 2016). "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. doi:10.1016/j.bbagen.2016.05.005. PMID 27155576.
  12. ^ "COQ5 Gene - Coenzyme Q5, Methyltransferase". GeneCards human gene database. Weizmann Institute of Science.
  13. ^ a b Dai YN, Zhou K, Cao DD, Jiang YL, Meng F, Chi CB, et al. (August 2014). "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. doi:10.1107/s1399004714011559. PMID 25084328.
  14. ^ Huang CC, Smith CV, Glickman MS, Jacobs WR, Sacchettini JC (March 2002). "Crystal structures of mycolic acid cyclopropane synthases from Mycobacterium tuberculosis". The Journal of Biological Chemistry. 277 (13): 11559–11569. doi:10.1074/jbc.m111698200. PMID 11756461.