The arrangement and role of some of the amino acid residues in the beta-ketoacyl synthetase site of chicken liver fatty acid synthetase.

Stoops, James K; Henry, S J; Wakil, Salih J.

doi:10.1016/s0021-9258(17)44201-3

Cited by 22 publications

(12 citation statements)

References 18 publications

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“…When the fatty acid synthase was inhibited with [14C]dibromopropanone and the cross-linked enzyme was subjected to performic acid oxidation [Baeyer-Villeger reaction (Hassal, 1957)] followed by HC1 hydrolysis (Crestfield et al, 1963), equal amounts of 14C-labeled sulfones of (carboxymethyl)cysteine and (carboxymethyl)cysteamine were obtained, indicating that the residues involved in the cross-linking are cysteine-SH and pantetheine-SH of the prosthetic group. This conclusion was supported further by the isolation of secondary propyl thioether derivatives of cysteine and cysteamine as the major products after reduction of the [14C]dibromopropanone-cross-linked synthase with borohydride followed by HC1 hydrolysis (Stoops & Wakil, 1983).…”

mentioning

confidence: 83%

Fatty acid synthase, a proficient multifunctional enzyme

1989

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mentioning

confidence: 83%

Fatty acid synthase, a proficient multifunctional enzyme

1989

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“…Chemicals. Buffers were prepared from Baker reagentgrade salts, and pH was determined as described previously (Stoops et al, 1983). NADPH and acetyl-and malonyl-CoAs1 were purchased from P-L Biochemicals.…”

Section: Methodsmentioning

confidence: 99%

Yeast fatty acid synthase: structure to function relationship

Singh¹,

Wakil²,

Stoops³

1985

Biochemistry

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The yeast fatty acid synthase is a multifunctional enzyme composed of two nonidentical subunits in an alpha 6 beta 6 complex that is active in synthesizing fatty acids. The seven catalytic activities required for fatty acid synthesis are divided between the alpha and beta subunits such that the alpha 6 beta 6 complex has six complements of each activity. It has been proposed that these are organized into six centers for fatty acid synthesis. There are different opinions regarding the operation of these centers in the alpha 6 beta 6 complex, on view being that they are functionally independent and the other proposes half-sites activity for the complex. We have attempted to distinguish between these proposals by the most direct method of active site titration, i.e., quantitation of fatty acyl product in the absence of turnover. This was accomplished by using p-nitrophenyl thioacetate and thiophenyl malonate (in place of the coenzyme A analogues) as substrates along with NADPH, thereby depriving the yeast synthase of coenzyme A required to release product as fatty acyl coenzyme A. The amount of fatty acyl product formed was quantitated by gas-liquid chromatography, as well as by direct estimation of radioactivity in the product when p-nitrophenyl thio [1-14C] acetate was used as a substrate. In both cases, a stoichiometry of close to six was found for mole of fatty acid synthesized per mole of alpha 6 beta 6 complex. This indicates that there are six functional centers for fatty acid synthesis in the multifunctional yeast alpha 6 beta 6 fatty acid synthase and that these centers operate independently.(ABSTRACT TRUNCATED AT 250 WORDS)

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“…82 Specifically, the active site residues Cys, His and His are conserved in the Type I FAS. A lysine has also been implicated in catalysis, 83 and analysis of the sequence data and modeling of the rat ketosynthase domain onto the E. coli FabB suggests that the conserved Lys326 of the rat FAS is present in the active site. 81 However, in the type II elongation condensing enzymes, the amide group of the corresponding Lys (328 in E. coli FabB) forms a hydrogen bond (0.28 nm) with the backbone oxygen of His298.…”

Section: Type I Fas Ketoacyl Synthase Active Sitementioning

confidence: 99%

The Claisen condensation in biology

2002

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The mechanism for carbon-carbon bond formation used in the biosynthesis of natural products such as fatty acids and polyketides is a decarboxylating Claisen condensation. The enzymes that catalyze this reaction in various bacterial systems, collectively referred to as condensing enzymes, have been intensively studied in the past several decades, and members of the family have been crystallized. The condensing enzymes share a common 3-dimensional fold, first described for the biosynthetic thiolase I that catalyzes a non-decarboxylating Claisen condensation, although they share little similarity at the amino acid level. Their active sites, however, possess significant similarities. The initiation condensing enzymes use CoA primers and possess a catalytic triad of Cys, His, Asn; and the elongating condensing enzymes that exclusively use ACP thioesters have a triad of Cys, His, His. These active site differences affect the sensitivity of the respective enzymes to the antibiotics thiolactomycin and cerulenin. Different reaction mechanisms have been proposed for the condensing enzymes. This review covers the recent structural and mechanistic data to see if a unifying hypothesis for the reaction mechanism catalyzed by this important family of enzymes can be established.

show abstract

The arrangement and role of some of the amino acid residues in the beta-ketoacyl synthetase site of chicken liver fatty acid synthetase.

Cited by 22 publications

References 18 publications

Fatty acid synthase, a proficient multifunctional enzyme

Fatty acid synthase, a proficient multifunctional enzyme

Yeast fatty acid synthase: structure to function relationship

The Claisen condensation in biology

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