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
Aliases	COQ5, coenzyme Q5, methyltransferase, COQ10D9
External IDs	OMIM: 616359; MGI: 1098643; HomoloGene: 6559; GeneCards: COQ5; OMA:COQ5 - orthologs
Gene location (Human) Chr. Chromosome 12 (human)[1] Band 12q24.31 Start 120,503,279 bp[1] End 120,534,434 bp[1]
Gene location (Mouse) Chr. Chromosome 5 (mouse)[2] Band 5 F|5 56.03 cM Start 115,417,725 bp[2] End 115,435,031 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in muscle of thigh gastrocnemius muscle skeletal muscle tissue apex of heart right lobe of liver mucosa of transverse colon left ventricle right adrenal cortex islet of Langerhans gonad Top expressed in muscle of thigh Paneth cell digastric muscle sternocleidomastoid muscle interventricular septum motor neuron genital tubercle quadriceps femoris muscle vastus lateralis muscle temporal muscle More reference expression data BioGPS n/a
Gene ontology Molecular function methyltransferase activity transferase activity protein binding 2-octaprenyl-6-methoxy-1,4-benzoquinone methylase activity 2-decaprenyl-6-methoxy-1,4-benzoquinone methyltransferase activity Cellular component membrane mitochondrion mitochondrial inner membrane mitochondrial matrix protein-containing complex extrinsic component of mitochondrial inner membrane Biological process ubiquinone biosynthetic process methylation Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 84274 52064 Ensembl ENSG00000110871 ENSMUSG00000041733 UniProt Q5HYK3 Q9CXI0 RefSeq (mRNA) NM_032314 NM_026504 RefSeq (protein) NP_115690 NP_080780 Location (UCSC) Chr 12: 120.5 – 120.53 Mb Chr 5: 115.42 – 115.44 Mb PubMed search [3] [4]
Wikidata
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2-Methoxy-6-polyprenyl-1,4-benzoquinol methylase
Identifiers
EC no.	2.1.1.201
Databases
IntEnz	IntEnz view
BRENDA	BRENDA entry
ExPASy	NiceZyme view
KEGG	KEGG entry
MetaCyc	metabolic pathway
PRIAM	profile
PDB structures	RCSB PDB PDBe PDBsum
Gene Ontology	AmiGO / QuickGO
Search PMC articles PubMed articles NCBI proteins

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]