The animal fatty acid synthase: one gene, one polypeptide, seven enzymes

@article{Smith1994TheAF,
  title={The animal fatty acid synthase: one gene, one polypeptide, seven enzymes},
  author={S. Smith},
  journal={The FASEB Journal},
  year={1994},
  volume={8},
  pages={1248 - 1259}
}
  • S. Smith
  • Published 1 December 1994
  • Chemistry, Medicine
  • The FASEB Journal
The animal fatty acid synthase comprises two multifunctional polypeptide chains, each containing seven discrete functional domains, juxtaposed head‐to‐tail such that two separate centers for fatty acid assembly are formed at the subunit interface. The kinetics and specificities of the component enzymes are well adapted to ensure that, at each of the two centers, the iterative condensation of an acetyl moiety with successive malonyl moieties and complete reduction of the β‐keto intermediates… Expand
Structural and functional organization of the animal fatty acid synthase.
TLDR
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TLDR
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Structure and function of animal fatty acid synthase
TLDR
Analysis of FAS particle images by using a simultaneous multiple model single particle refinement method confirmed that FAS structure exists in various conformational states and predicted that the intersubunit hinge region and the intrasubunit hinge located between domains II and III are highly flexible. Expand
Chapter 6 Fatty acid synthesis in eukaryotes
TLDR
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TLDR
It is found that kallikrein cleavage sites occur in the least conserved regions of the FAS polypeptide subunit, and the order of the component activities in domain I is confirmed, paving the way for successful expression and characterization of the remaining activities. Expand
Uncovering the molecular basis for fatty acid synthase product specificity: Structural and kinetic evaluation of thioesterase I and thioesterase II
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TLDR
The crystal structure is reported here the crystal structure of the malonyl-CoA specific transferase from Escherichia coli, which has an α/β type architecture, but its fold is unique. Expand
Engineering of an active animal fatty acid synthase dimer with only one competent subunit.
TLDR
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Human fatty acid synthase: Role of interdomain in the formation of catalytically active synthase dimer
TLDR
It is shown that the fatty acid synthase activity could not be reconstituted when the ID sequences present in the two recombinant halves are deleted, suggesting that these ID sequences are essential for fatty Acid synthase dimer formation. Expand
Human fatty acid synthase: structure and substrate selectivity of the thioesterase domain.
TLDR
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References

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The architecture of the animal fatty acid synthetase complex. IV. Mapping of active centers and model for the mechanism of action.
TLDR
A functional model is proposed based on the aforementioned results and the recent evidence that the synthetase subunits are arranged in a head-to-tail fashion, such that the pantetheine-SH of the acyl carrier protein of one subunit and the cysteine- SH of the beta-ketoacyl synthetases of the second subunit are juxtaposed. Expand
Mammalian fatty acid synthetase is a structurally and functionally symmetrical dimer.
TLDR
After assembly of long-chain acyl moieties on the 4'-phosphopantetheine residues, no vacant condensing-enzyme active sites were demonstrable either by cross-linking with 1,3-dibromo-2-propanone or by formation of carboxymethylcysteamine on treatment with iodoacetate. Expand
Structural organization of the multifunctional animal fatty-acid synthase.
TLDR
The data permit refinement of the model for the fatty-acid synthase dimer and suggest that the malonyl/acetyl transferase and oxoacyl synthase of one subunit cooperate with the reductases, acyl carrier protein and thioesterase of the companion subunit in the formation of a center for fatty- acid synthesis. Expand
Construction, expression, and characterization of a mutated animal fatty acid synthase deficient in the dehydrase function.
TLDR
Examination of the completed domain map for the animal fatty acid synthase indicates that the catalytic domains are clustered in two groups separated by a central structural core: the ketoacyl synthase, malonyl/acetyltransferase, and dehydrase in the amino-terminal half and the enoyl reductase, ketoreductase, acyl carrier protein, and thioesterase in the carboxyl- terminus of the transferase domain. Expand
Rat mammary gland fatty acid synthase: localization of the constituent domains and two functional polyadenylation/termination signals in the cDNA.
TLDR
Comparison of FAS from different sources shows that the primary sequence is conserved only for the active residues and the amino acids in their immediate vicinity. Expand
Isolation of a functional transferase component from the rat fatty acid synthase by limited trypsinization of the subunit monomer. Formation of a stable functional complex between transferase and acyl carrier protein domains.
TLDR
The results provide the first direct evidence that, in the head-to-tail oriented fatty acid synthase homodimer, functional communication between the transferase domain located near the end of one polypeptide and the acyl carrier protein domain located at the opposite end of the other polyPEptide is facilitated by a stable physical interaction between these domains. Expand
Synthesis of long chain acyl-enzyme thioesters by modified fatty acid synthetases and their hydrolysis by a mammary gland thioesterase.
TLDR
The ability of thioesterase II to modify the product specificity of normal fatty acid synthetase is most likely attributable to the capacity of thiodinease II for hydrolysis of acyl moieties fromThioester linkage to the multienzyme. Expand
Amino acid sequence around the active serine in the acyl transferase domain of rabbit mammary fatty acid synthase
TLDR
Rabbit mammary fatty acid synthase was labelled in the acyl transferase domain(s) by the formation of the O‐ester intermediates after incubation with [14C]acetyl‐ or malonyl‐CoA, confirming the hypothesis that, unlike Escherichia coli or yeast, a single transferase catalyses the transfer of both acetyl‐ and maloneyl‐groups in the mammalian complex. Expand
Organization of the enzymatic domains in the multifunctional polyketide synthase involved in erythromycin formation in Saccharopolyspora erythraea.
TLDR
Comparison of the six synthase units (SU) from the eryA genes with each other and with mono- and multifunctional fatty acid and polyketide synthases established the extent of each beta-ketoacyl acyl-carrier protein (ACP) synthase, acyltransferase,beta-ketoreductase, ACP, and thioesterase domain. Expand
Intron-exon organization of the gene for the multifunctional animal fatty acid synthase.
The complete intron-exon organization of the gene encoding a multifunctional mammalian fatty acid synthase has been elucidated, and specific exons have been assigned to coding sequences for theExpand
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