Lonhienne Thierry, Garcia Mario D, Fraser James A, Williams Craig M, Guddat Luke W
The School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD, Australia.
PLoS One. 2017 Feb 8;12(2):e0171443. doi: 10.1371/journal.pone.0171443. eCollection 2017.
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.
乙酰羟酸合酶（AHAS）催化支链氨基酸生物合成的第一步，这是一条对植物和微生物生命周期至关重要的途径。催化亚基以硫胺素二磷酸（ThDP）和黄素腺嘌呤二核苷酸（FAD）作为不可或缺的辅因子。酿酒酵母AHAS的一种新的高分辨率2.0埃晶体结构表明，二聚体是不对称的，催化中心具有不同的结构，其中FAD被困在两种不同的构象中，表明存在不同的氧化还原状态。每个活性位点表面结合有两个氧分子（O2），多肽中的一条通道似乎能将O2独立于底物传递到活性位点。因此，O2似乎在这种酶中发挥着一种新的“辅因子”作用。我们讨论了该酶这些此前未被描述的特征的功能意义。
