Enzyme found in humans
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]
Function
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
Catalyzes C-methylation and ubiquinone biosynthetic process.[12]
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.[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]