Crystal structures and catalytic mechanism of the C-methyltransferase Coq5 provide insights into a key step of the yeast coenzyme Q synthesis pathway.
Acta Crystallogr D Biol Crystallogr
; 70(Pt 8): 2085-92, 2014 Aug.
Article
em En
| MEDLINE
| ID: mdl-25084328
ABSTRACT
Saccharomyces cerevisiae Coq5 is an S-adenosyl methionine (SAM)-dependent methyltransferase (SAM-MTase) that catalyzes the only C-methylation step in the coenzyme Q (CoQ) biosynthesis pathway, in which 2-methoxy-6-polyprenyl-1,4-benzoquinone (DDMQH2) is converted to 2-methoxy-5-methyl-6-polyprenyl-1,4-benzoquinone (DMQH2). Crystal structures of Coq5 were determined in the apo form (Coq5-apo) at 2.2â
Å resolution and in the SAM-bound form (Coq5-SAM) at 2.4â
Å resolution, representing the first pair of structures for the yeast CoQ biosynthetic enzymes. Coq5 displays a typical class I SAM-MTase structure with two minor variations beyond the core domain, both of which are considered to participate in dimerization and/or substrate recognition. Slight conformational changes at the active-site pocket were observed upon binding of SAM. Structure-based computational simulation using an analogue of DDMQH2 enabled us to identify the binding pocket and entrance tunnel of the substrate. Multiple-sequence alignment showed that the residues contributing to the dimeric interface and the SAM- and DDMQH2-binding sites are highly conserved in Coq5 and homologues from diverse species. A putative catalytic mechanism of Coq5 was proposed in which Arg201 acts as a general base to initiate catalysis with the help of a water molecule.
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Assunto principal:
Saccharomyces cerevisiae
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Ubiquinona
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Cristalografia por Raios X
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Proteínas de Saccharomyces cerevisiae
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Metiltransferases
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article