The 2.0 Å X-ray structure for yeast acetohydroxyacid synthase provides new insights into its cofactor and quaternary structure requirements.
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 (O2) are bound on the surface of each active site and a tunnel in the polypeptide appears to passage O2 to the active site independently of the substrate. Thus, O2 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.
The School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD, Australia.
Thierry
T
Lonhienne
The School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD, Australia.
Mario D
MD
Garcia
The School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD, Australia.
James A
JA
Fraser
The School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD, Australia.
Craig M
CM
Williams
The School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD, Australia.
Luke W
LW
Guddat
D000095:Acetolactate Synthase / Q000737:chemistry* / Q000378:metabolism; D000595:Amino Acid Sequence; D002384:Catalysis; D005182:Flavin-Adenine Dinucleotide / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D010084:Oxidation-Reduction; D010100:Oxygen / Q000737:chemistry; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D012441:Saccharomyces cerevisiae / Q000201:enzymology*
D005182:Flavin-Adenine Dinucleotide; D000095:Acetolactate Synthase; D010100:Oxygen