Crystal structure of yeast acetyl-coenzyme A synthetase in complex with AMP.
Acetyl-coenzyme A synthetase (ACS) belongs to the family of AMP-forming enzymes that also includes acyl-CoA synthetases, firefly luciferase, and nonribosomal peptide synthetases. ACS catalyzes the two-step activation of acetate to acetyl-CoA: formation of an acetyl-AMP intermediate from acetate and ATP and the transfer of the acetyl group to CoA. In mammals, the acetyl-CoA product is used for biosynthesis of long chain fatty acids as well as energy production. We have determined the crystal structure of yeast ACS in a binary complex with AMP at 2.3 A resolution. The structure contains a large, N-terminal domain and a small, C-terminal domain. AMP is bound at the interface between the two domains. This structure represents a new conformation for the ACS enzyme, which may be competent for catalyzing the first step of the reaction. A Lys residue that is critical for this step is located in the active site. A rotation of 140 degrees in the small domain is needed for the binding of CoA and the catalysis of the second step. In contrast to the monomeric bacterial enzyme, yeast ACS is a stable trimer.
Jogl
Gerwald
G
Department of Biological Sciences, Columbia University, New York, New York 10027, USA.
Tong
Liang
L
D000106:Acetate-CoA Ligase / Q000737:chemistry*; D000249:Adenosine Monophosphate / Q000737:chemistry*; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry; D001665:Binding Sites; D002384:Catalysis; D003460:Crystallization; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry*; D019779:Salmonella enterica / Q000737:chemistry; D017386:Sequence Homology, Amino Acid
D001426:Bacterial Proteins; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins; D000249:Adenosine Monophosphate; D000106:Acetate-CoA Ligase