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Structure paper

TitleDiscovery of a Regulatory Subunit of the Yeast Fatty Acid Synthase.
Journal, issue, pagesCell, Vol. 180, Issue 6, Page 1130-1143.e20, Year 2020
Publish dateMar 19, 2020
AuthorsKashish Singh / Benjamin Graf / Andreas Linden / Viktor Sautner / Henning Urlaub / Kai Tittmann / Holger Stark / Ashwin Chari /
PubMed AbstractFatty acid synthases (FASs) are central to metabolism but are also of biotechnological interest for the production of fine chemicals and biofuels from renewable resources. During fatty acid ...Fatty acid synthases (FASs) are central to metabolism but are also of biotechnological interest for the production of fine chemicals and biofuels from renewable resources. During fatty acid synthesis, the growing fatty acid chain is thought to be shuttled by the dynamic acyl carrier protein domain to several enzyme active sites. Here, we report the discovery of a γ subunit of the 2.6 megadalton α-βS. cerevisiae FAS, which is shown by high-resolution structures to stabilize a rotated FAS conformation and rearrange ACP domains from equatorial to axial positions. The γ subunit spans the length of the FAS inner cavity, impeding reductase activities of FAS, regulating NADPH turnover by kinetic hysteresis at the ketoreductase, and suppressing off-pathway reactions at the enoylreductase. The γ subunit delineates the functional compartment within FAS. As a scaffold, it may be exploited to incorporate natural and designed enzymatic activities that are not present in natural FAS.
External linksCell / PubMed:32160528
MethodsEM (single particle) / X-ray diffraction
Resolution2.8 - 4.6 Å
Structure data

4577

6ql5

EMDB-4577, PDB-6ql5:
Structure of fatty acid synthase complex with bound gamma subunit from Saccharomyces cerevisiae at 2.8 angstrom
Method: EM (single particle) / Resolution: 2.8 Å

4578

6ql6

EMDB-4578, PDB-6ql6:
Structure of Fatty acid synthase complex from Saccharomyces cerevisiae at 2.9 Angstrom
Method: EM (single particle) / Resolution: 2.9 Å

PDB-6ql7:
Structure of fatty acid synthase complex with bound gamma subunit from Saccharomyces cerevisiae at 4.6 angstrom
Method: X-RAY DIFFRACTION / Resolution: 4.6 Å

PDB-6ql9:
Structure of Fatty acid synthase complex from Saccharomyces cerevisiae at 2.9 Angstrom
Method: X-RAY DIFFRACTION / Resolution: 2.82 Å

Chemicals

ChemComp-PNS:
4'-PHOSPHOPANTETHEINE / Phosphopantetheine

ChemComp-FMN:
FLAVIN MONONUCLEOTIDE / Flavin mononucleotide

ChemComp-J8T:
[(3~{R})-4-azanyl-2,2-dimethyl-3-oxidanyl-4-oxidanylidene-butyl] dihydrogen phosphate

ChemComp-EDO:
1,2-ETHANEDIOL / Ethylene glycol

ChemComp-NA:
Unknown entry

ChemComp-A2P:
ADENOSINE-2'-5'-DIPHOSPHATE / Adenosine diphosphate

ChemComp-ACT:
ACETATE ION / Acetate

ChemComp-PGE:
TRIETHYLENE GLYCOL / Polyethylene glycol

ChemComp-MLI:
MALONATE ION / Malonic acid

ChemComp-HOH:
WATER / Water

Source
  • saccharomyces cerevisiae (brewer's yeast)
  • Baker's yeast (brewer's yeast)
  • saccharomyces cerevisiae (strain atcc 204508 / s288c) (yeast)
KeywordsTRANSFERASE / Fatty acid synthase / Acyl carrier protein / Ketosynthase / Ketoreductase / Enoyl reductase / Dehydratase / Malonyl/palmitoyl transferase / Acetyl transferase / Phosphopantetheine transferase

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