DOI: 10.1126/science.1138249. Structural Basis for Substrate Delivery by Acyl Carrier Protein in the Yeast Fatty Acid Synthase

Structural Basis for Substrate Delivery by Acyl Carrier Protein in the Yeast Fatty Acid Synthase

10.1126/science.1138249

Crossref journal-article

American Association for the Advancement of Science (AAAS)

Science (221)

Abstract

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.

Bibliography

Leibundgut, M., Jenni, S., Frick, C., & Ban, N. (2007). Structural Basis for Substrate Delivery by Acyl Carrier Protein in the Yeast Fatty Acid Synthase. Science, 316(5822), 288â290.

Authors 4

Marc Leibundgut (first)
Simon Jenni (additional)
Christian Frick (additional)
Nenad Ban (additional)

References 31 Referenced 171

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All data were collected at the Swiss Light Source (SLS Paul Scherrer Institute Villigen). We are grateful to C. Schulze-Briese S. Gutmann E. Pohl S. Russo and T. Tomizaki for their outstanding support at the SLS. We thank T. Maier and J. Erzberger for critically reading the manuscript and all members of the Ban laboratory for suggestions and discussions; R. Grosse-Kunstleve P. Afonine and P. Adams for providing a prerelease version of the PHENIX refinement program and advice regarding structure refinement; A. Jones for a prerelease version of the program O; D. Sargent for technical assistance. Yeast cells were kindly provided by F. Hepfer of Hefe Schweiz AG. This work was supported by the Swiss National Science Foundation (SNSF) and the National Center of Excellence in Research (NCCR) Structural Biology program of the SNSF. Coordinates and structure factors of the S. cerevisiae structure have been deposited in the Protein Data Bank with the accession code 2UV8.

Dates

Type	When
Created	18 years, 4 months ago (April 12, 2007, 6:08 p.m.)
Deposited	1 year, 7 months ago (Jan. 10, 2024, 3:45 a.m.)
Indexed	1 month, 4 weeks ago (July 7, 2025, 3:44 p.m.)
Issued	18 years, 4 months ago (April 13, 2007)
Published	18 years, 4 months ago (April 13, 2007)
Published Print	18 years, 4 months ago (April 13, 2007)

Funders 0

None

BibTeX

@article{Leibundgut_2007, title={Structural Basis for Substrate Delivery by Acyl Carrier Protein in the Yeast Fatty Acid Synthase}, volume={316}, ISSN={1095-9203}, url={http://dx.doi.org/10.1126/science.1138249}, DOI={10.1126/science.1138249}, number={5822}, journal={Science}, publisher={American Association for the Advancement of Science (AAAS)}, author={Leibundgut, Marc and Jenni, Simon and Frick, Christian and Ban, Nenad}, year={2007}, month=apr, pages={288–290} }

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