Crystal structures and catalytic mechanism of the C‐methyltransferase Coq5 provide insights into a key step of the yeast coenzyme Q synthesis pathway. (1st August 2014)

• Record Type: Journal Article
• Authors: Dai, Ya‐Nan; Zhou, Kang; Cao, Dong‐Dong; Jiang, Yong‐Liang; Meng, Fei; Chi, Chang‐Biao; Ren, Yan‐Min; Chen, Yuxing; Zhou, Cong‐Zhao
• Is Part Of: Acta crystallographica. Volume 70:Part 8(2014:Aug.)
• Page Start: 2085
• Page End: 2092
• Publication Date: 2014-08-01
• Subjects: Biomolecules -- Structure -- Periodicals; Physical biochemistry -- Periodicals; X-ray crystallography -- Periodicals; Crystallography -- Periodicals; 572
• DOI: 10.1107/S1399004714011559
• Languages: English
• ISSNs: 0907-4449

Abstract

<abstract abstract-type="main" xml:lang="en"> <title> <x xml:space="preserve">Abstract</x> </title> <p> <italic>Saccharomyces cerevisiae</italic> Coq5 is an <italic>S</italic>‐adenosyl methionine (SAM)‐dependent methyltransferase (SAM‐MTase) that catalyzes the only <italic>C</italic>‐methylation step in the coenzyme Q (CoQ) biosynthesis pathway, in which 2‐methoxy‐6‐polyprenyl‐1, 4‐benzoquinone (DDMQH<sub>2</sub>) is converted to 2‐methoxy‐5‐methyl‐6‐polyprenyl‐1, 4‐benzoquinone (DMQH<sub>2</sub>). Crystal structures of Coq5 were determined in the apo form (Coq5‐apo) at 2.2 Å resolution and in the SAM‐bound form (Coq5‐SAM) at 2.4 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 DDMQH<sub>2</sub> 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 DDMQH<sub>2</sub>‐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.</p> </abstract>