Structural basis for substrate delivery by acyl carrier protein in the yeast fatty acid synthase.
In the multifunctional fungal fatty acid synthase (FAS), the acyl carrier protein (ACP) domain shuttles reaction intermediates covalently attached to its prosthetic phosphopantetheine group between the different enzymatic centers of the reaction cycle. Here, we report the structure of the Saccharomyces cerevisiae FAS determined at 3.1 angstrom resolution with its ACP stalled at the active site of ketoacyl synthase. The ACP contacts the base of the reaction chamber through conserved, charge-complementary surfaces, which optimally position the ACP toward the catalytic cleft of ketoacyl synthase. The conformation of the prosthetic group suggests a switchblade mechanism for acyl chain delivery to the active site of the enzyme.
Leibundgut
Marc
M
Institute of Molecular Biology and Biophysics, ETH Zurich, 8092 Zurich, Switzerland.
Jenni
Simon
S
Frick
Christian
C
Ban
Nenad
N
D000213:Acyl Carrier Protein / Q000737:chemistry* / Q000378:metabolism; D000217:Acyltransferases / Q000378:metabolism; D000595:Amino Acid Sequence; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D064429:Fatty Acid Synthases / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000378:metabolism
D000213:Acyl Carrier Protein; D029701:Saccharomyces cerevisiae Proteins; D000217:Acyltransferases; D064429:Fatty Acid Synthases