The 2.0 Å X-ray structure for yeast acetohydroxyacid synthase provides new insights into its cofactor and quaternary structure requirements

Lonhienne, Thierry, Garcia, Mario D., Fraser, James A., Williams, Craig M. and Guddat, Luke W. (2017) The 2.0 Å X-ray structure for yeast acetohydroxyacid synthase provides new insights into its cofactor and quaternary structure requirements. PLoS One, 12 2: e0171443.1-e0171443.13. doi:10.1371/journal.pone.0171443


Author Lonhienne, Thierry
Garcia, Mario D.
Fraser, James A.
Williams, Craig M.
Guddat, Luke W.
Title The 2.0 Å X-ray structure for yeast acetohydroxyacid synthase provides new insights into its cofactor and quaternary structure requirements
Journal name PLoS One   Check publisher's open access policy
ISSN 1932-6203
Publication date 2017-02-08
Sub-type Article (original research)
DOI 10.1371/journal.pone.0171443
Open Access Status DOI
Volume 12
Issue 2
Start page e0171443.1
End page e0171443.13
Total pages 13
Place of publication San Francisco, CA, United States
Publisher Public Library of Science
Language eng
Subject 2700 Medicine
1300 Biochemistry, Genetics and Molecular Biology
1100 Agricultural and Biological Sciences
Abstract 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 ) are bound on the surface of each active site and a tunnel in the polypeptide appears to passage O to the active site independently of the substrate. Thus, O 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.
Formatted abstract
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.
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID 1008736
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: School of Chemistry and Molecular Biosciences
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Created: Fri, 10 Feb 2017, 11:13:18 EST by Mrs Louise Nimwegen on behalf of School of Chemistry & Molecular Biosciences