Allosteric Mechanisms in ACT Domain Containing Enzymes Involved in Amino Acid Metabolism

Amino Acids. 2005 Feb;28(1):1-12. doi: 10.1007/s00726-004-0152-y. Epub 2005 Jan 18.

Abstract

An important sequence motif identified by sequence analysis is shared by the ACT domain family, which has been found in a number of diverse proteins. Most of the proteins containing the ACT domain seem to be involved in amino acid and purine synthesis and are in many cases allosteric enzymes with complex regulation enforced by the binding of ligands. Here we explore the current understanding of the ACT domain function including its role as an allosteric module in a selected group of enzymes. We will further describe in more detail three of the proteins where some understanding is available on function and structure: i) the archetypical ACT domain protein E. coli 3PGDH, which catalyzes the first step in the biosynthesis of L-Ser, ii) the bifunctional chorismate mutase/prephenate dehydratase (P-protein) from E. coli, which catalyzes the first two steps in the biosynthesis of L-Phe, and iii) the mammalian aromatic amino acid hydroxylases, with special emphasis on phenylalanine hydroxylase, which catalyzes the first step in the catabolic degradation of L-phenylalanine (L-Phe). The ACT domain is commonly involved in the binding of a small regulatory molecule, such as the amino acids L-Ser and L-Phe in the case of 3PGDH and P-protein, respectively. On the other hand, for PAH, and probably for other enzymes, this domain appears to have been incorporated as a handy, flexible small module with the potential to provide allosteric regulation via transmission of finely tuned conformational changes, not necessarily initiated by regulatory ligand binding at the domain itself.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Allosteric Regulation
  • Allosteric Site
  • Amino Acid Motifs
  • Amino Acid Sequence
  • Amino Acids / metabolism*
  • Animals
  • Carbohydrate Dehydrogenases / chemistry
  • Carbohydrate Dehydrogenases / metabolism
  • Chorismate Mutase / chemistry
  • Chorismate Mutase / metabolism
  • Enzymes / chemistry*
  • Enzymes / metabolism*
  • Escherichia coli Proteins / chemistry
  • Escherichia coli Proteins / metabolism
  • Evolution, Molecular
  • Mixed Function Oxygenases / chemistry
  • Mixed Function Oxygenases / metabolism
  • Molecular Sequence Data
  • Multienzyme Complexes / chemistry
  • Multienzyme Complexes / metabolism
  • Phosphoglycerate Dehydrogenase
  • Prephenate Dehydratase / chemistry
  • Prephenate Dehydratase / metabolism
  • Protein Structure, Tertiary

Substances

  • Amino Acids
  • Enzymes
  • Escherichia coli Proteins
  • Multienzyme Complexes
  • P-protein, E coli
  • Mixed Function Oxygenases
  • Carbohydrate Dehydrogenases
  • Phosphoglycerate Dehydrogenase
  • Prephenate Dehydratase
  • Chorismate Mutase