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]
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]
^ abChen 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. PMID23354120.
^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. PMID27155576.
^ abDai 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. PMID25084328.
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