The 1.75 A crystal structure of acetyl-CoA synthetase bound to adenosine-5'-propylphosphate and coenzyme A

Biochemistry. 2003 Mar 18;42(10):2866-73. doi: 10.1021/bi0271603.


Acetyl-coenzyme A synthetase catalyzes the two-step synthesis of acetyl-CoA from acetate, ATP, and CoA and belongs to a family of adenylate-forming enzymes that generate an acyl-AMP intermediate. This family includes other acyl- and aryl-CoA synthetases, firefly luciferase, and the adenylation domains of the modular nonribosomal peptide synthetases. We have determined the X-ray crystal structure of acetyl-CoA synthetase complexed with adenosine-5'-propylphosphate and CoA. The structure identifies the CoA binding pocket as well as a new conformation for members of this enzyme family in which the approximately 110-residue C-terminal domain exhibits a large rotation compared to structures of peptide synthetase adenylation domains. This domain movement presents a new set of residues to the active site and removes a conserved lysine residue that was previously shown to be important for catalysis of the adenylation half-reaction. Comparison of our structure with kinetic and structural data of closely related enzymes suggests that the members of the adenylate-forming family of enzymes may adopt two different orientations to catalyze the two half-reactions. Additionally, we provide a structural explanation for the recently shown control of enzyme activity by acetylation of an active site lysine.

Publication types

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

MeSH terms

  • Acetate-CoA Ligase / chemistry*
  • Acetate-CoA Ligase / isolation & purification
  • Acetylation
  • Acyl Coenzyme A / chemistry
  • Adenosine Monophosphate / chemistry*
  • Amino Acid Sequence
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / isolation & purification
  • Binding Sites
  • Binding, Competitive
  • Coenzyme A / chemistry*
  • Coenzyme A Ligases / antagonists & inhibitors
  • Coenzyme A Ligases / chemistry
  • Crystallization
  • Crystallography, X-Ray
  • Enzyme Inhibitors / chemistry
  • Molecular Sequence Data
  • Protein Conformation
  • Salmonella enterica / enzymology


  • Acyl Coenzyme A
  • Bacterial Proteins
  • Enzyme Inhibitors
  • propionyl-coenzyme A
  • Adenosine Monophosphate
  • Coenzyme A Ligases
  • Acetate-CoA Ligase
  • propionate - CoA ligase
  • Coenzyme A

Associated data

  • PDB/1NNM
  • PDB/1NNN