High Resolution Crystal Structures of the Acetohydroxyacid Synthase‐Pyruvate Complex Provide New Insights into Its Catalytic Mechanism

Abstract:

Acetohydroxyacid synthase (AHAS) is the first enzyme in the biosynthesis pathway of the branched‐chain amino acids, catalyzing the condensation of pyruvate with another molecule of pyruvate or with 2‐ketobutyrate, to produce 2‐acetolactate or 2‐acetohydroxybutyrate, respectively. The catalytic subunit of the dimeric enzyme has thiamin diphosphate (ThDP), a divalent metal ion, flavin adenine dinucleotide (FAD), and two molecules of oxygen (O2(I) and O2(II)) as cofactors. Here, crystal structures of Saccharomyces cerevisiae AHAS in complex with pyruvate provide novel insights into the mechanistic features of this enzyme including: i) The precise position taken by pyruvate molecules as they enter the active site (i. e. prior to catalysis occurring) with conformations suitable for the transfer of electrons to/from O2(I) and FAD; ii) The formation of ternary donor‐acceptor‐O2(I) complexes and iii) The location of O2(II …

Año de publicación:

2017

Keywords:

Fuente:

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