Open AccessThe 2.0 Å X-ray structure for yeast acetohydroxyacid synthase provides new insights into its cofactor and quaternary structure requirements
Author(s) -
Thierry Lonhienne,
Mario D. García,
James A. Fraser,
Craig M. Williams,
Luke W. Guddat
Publication year - 2017
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0171443
Subject(s) - cofactor , active site , flavin adenine dinucleotide , oxidoreductase , dimer , enzyme , saccharomyces cerevisiae , biochemistry , stereochemistry , chemistry , protein quaternary structure , biosynthesis , atp synthase , flavin mononucleotide , catalytic cycle , yeast , protein subunit , gene , organic chemistry
Acetohydroxyacid synthase (AHAS) catalyzes the first step of branched-chain amino acid biosynthesis, a pathway essential to the life-cycle of plants and micro-organisms. The catalytic subunit has thiamin diphosphate (ThDP) and flavin adenine dinucleotide (FAD) as indispensable co-factors. A new, high resolution, 2.0 Å crystal structure of Saccharomyces cerevisiae AHAS reveals that the dimer is asymmetric, with the catalytic centres having distinct structures where FAD is trapped in two different conformations indicative of different redox states. Two molecules of oxygen (O 2 ) are bound on the surface of each active site and a tunnel in the polypeptide appears to passage O 2 to the active site independently of the substrate. Thus, O 2 appears to play a novel “co-factor” role in this enzyme. We discuss the functional implications of these features of the enzyme that have not previously been described.