Allosteric regulation in Acetohydroxyacid Synthases (AHASs) - Different structures and kinetic behavior in isozymes in the same organisms

Ze'ev Barak, David M. Chipman

Research output: Contribution to journalReview articlepeer-review

24 Scopus citations

Abstract

Acetohydroxyacid Synthases (AHASs) have separate small regulatory subunits which specifically activate the catalytic subunits with which they are associated. The binding sites for the inhibitory amino acid(s) (valine or leucine) are in the interface between two ACT (small ligand binding) domains, and are apparently found in all AHAS regulatory subunits. However, the structures and the kinetic mechanisms of the different enzymes are very heterogeneous. Among the three isozymes encoded in the enterobacteria, the regulatory patterns are different, and their different responses to the inhibitory end product valine can be rationalized, at least in part, on the basis of the regulatory subunit structures and differences in catalytic mechanisms. The regulatory subunits in "typical" single AHASs found in other bacteria are similar to that of Escherichia coli isozyme AHAS III. Eukaryotic AHASs have more complex regulatory mechanisms and larger regulatory subunits. Such AHASs have two separate ACT sequence domains on the same regulatory polypeptide and can simultaneously bind two amino acids with synergistic effects. Yeast and fungal AHASs have ATP-binding sequence inserts in their regulatory subunits and are activated by MgATP in addition to being inhibited by valine.

Original languageEnglish
Pages (from-to)167-174
Number of pages8
JournalArchives of Biochemistry and Biophysics
Volume519
Issue number2
DOIs
StatePublished - 15 Mar 2012

Keywords

  • ACT domain
  • Acetohydroxyacid Synthase
  • Mutagenesis
  • Regulatory subunit
  • Thiamin diphosphate
  • Valine regulation

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

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