The multifaceted pyridoxal 5′-phosphate-dependent O-acetylserine sulfhydrylase

Mozzarelli, Andrea; Bettati, Stefano; Campanini, Barbara; Salsi, Enea; Raboni, Samanta; Singh, Ratna; Spyrakis, Francesca; Kumar, Vidya P.; Cook, Paul F.

doi:10.1016/j.bbapap.2011.04.011

Cited by 42 publications

(58 citation statements)

References 96 publications

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“…O-Acetylserine sulfhydrylase is an enzyme that catalyzes L-cysteine synthesis using L-OAS and sulfide (23,24), which is the last step in L-cysteine biosynthesis, whereas cystathionine ␤-synthase synthesizes cystathionine using L-serine and L-homocysteine in the transsulfuration pathway from L-methionine to L-cysteine (25,26). These enzymes commonly require pyridoxal 5=-phosphate (PLP) as a cofactor to express the catalytic activity.…”

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confidence: 99%

Establishment of anIn Vitrod-Cycloserine-Synthesizing System by UsingO-Ureido-l-Serine Synthase andd-Cycloserine Synthetase Found in the Biosynthetic Pathway

Uda

Matoba

Kumagai

et al. 2013

Antimicrob Agents Chemother

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We have recently cloned a DNA fragment containing a gene cluster that is responsible for the biosynthesis of an antituberculosis antibiotic, D-cycloserine. The gene cluster is composed of 10 open reading frames, designated dcsA to dcsJ. Judging from the sequence similarity between each putative gene product and known proteins, DcsC, which displays high homology to diaminopimelate epimerase, may catalyze the racemization of O-ureidoserine. DcsD is similar to O-acetylserine sulfhydrylase, which generates L-cysteine using O-acetyl-L-serine with sulfide, and therefore, DcsD may be a synthase to generate O-ureido-L-serine using O-acetyl-L-serine and hydroxyurea. DcsG, which exhibits similarity to a family of enzymes with an ATP-grasp fold, may be an ATP-dependent synthetase converting O-ureido-D-serine into D-cycloserine. In the present study, to characterize the enzymatic functions of DcsC, DcsD, and DcsG, each protein was overexpressed in Escherichia coli and purified to near homogeneity. The biochemical function of each of the reactions catalyzed by these three proteins was verified by thin-layer chromatography (TLC), high-performance liquid chromatography (HPLC), and, in some cases, mass spectrometry. The results from this study demonstrate that by using a mixture of the three purified enzymes and the two commercially available substrates O-acetyl-L-serine and hydroxyurea, synthesis of D-cycloserine was successfully attained. These in vitro studies yield the conclusion that DcsD and DcsG are necessary for the syntheses of O-ureido-L-serine and D-cycloserine, respectively. DcsD was also able to catalyze the synthesis of L-cysteine when sulfide was added instead of hydroxyurea. Furthermore, the present study shows that DcsG can also form other cyclic D-amino acid analogs, such as D-homocysteine thiolactone.

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confidence: 99%

Establishment of anIn Vitrod-Cycloserine-Synthesizing System by UsingO-Ureido-l-Serine Synthase andd-Cycloserine Synthetase Found in the Biosynthetic Pathway

Uda

Matoba

Kumagai

et al. 2013

Antimicrob Agents Chemother

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“…Furthermore, PLP-dependent enzymes play key roles in many pathways. For example, most sulfur in plants is incorporated by the reductive sulfate assimilation pathway in which the last enzyme (O-acetylserine sulfhydrylase) is PLP-dependent (Mozzarelli et al 2011). PLPdependent enzymes, SHMT and GDC, catalyze the methylation of THF through the serine/glycine pair, and hence are one of the bases of one-carbon (C 1 ) metabolism, linking amino acid and folate metabolism (Schirch and Szebenyi 2005), and participating as well in photorespiration (Jamai et al 2009).…”

Section: Biochemical Function and Its Impact On Plant Metabolismmentioning

confidence: 98%

Plant amino acid-derived vitamins: biosynthesis and function

Miret

Munné‐Bosch

2013

Amino Acids

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Vitamins are essential organic compounds for humans, having lost the ability to de novo synthesize them. Hence, they represent dietary requirements, which are covered by plants as the main dietary source of most vitamins (through food or livestock's feed). Most vitamins synthesized by plants present amino acids as precursors (B1, B2, B3, B5, B7, B9 and E) and are therefore linked to plant nitrogen metabolism. Amino acids play different roles in their biosynthesis and metabolism, either incorporated into the backbone of the vitamin or as amino, sulfur or one-carbon group donors. There is a high natural variation in vitamin contents in crops and its exploitation through breeding, metabolic engineering and agronomic practices can enhance their nutritional quality. While the underlying biochemical roles of vitamins as cosubstrates or cofactors are usually common for most eukaryotes, the impact of vitamins B and E in metabolism and physiology can be quite different on plants and animals. Here, we first aim at giving an overview of the biosynthesis of amino acid-derived vitamins in plants, with a particular focus on how this knowledge can be exploited to increase vitamin contents in crops. Second, we will focus on the functions of these vitamins in both plants and animals (and humans in particular), to unravel common and specific roles for vitamins in evolutionary distant organisms, in which these amino acid-derived vitamins play, however, an essential role.

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“…After cooling, the benzene was decanted, and the acqueous phases was extracted with dichloromethane (3 Â 20 mL), acidified with 2N HCl to pH 2 and extracted again with ethyl acetate (3 Â 10 mL). The combined organic layers were then washed with brine, dried over MgSO 4 and concentrated under reduced pressure. The crude residue was purified by flash chromatography eluting with petroleum ether/ ethyl acetate (90:10), to give the desired product as a white solid in 35% overall yield.…”

Section: General Procedures For the Synthesis Of Derivatives 19-24mentioning

confidence: 99%

“…The former catalyzes the transfer of an acetyl group from acetyl-CoA to the hydroxyl of L-serine, leading to the formation of an activated form of serine, O-acetyl-L-serine (OAS) and CoA-SH. The latter enzyme catalyzes a two-step reaction: in the first half-reaction, an a-aminoacrylate is formed upon b-elimination of substituted L-serine; in the second halfreaction, the a-aminoacrylate is attacked by sulfide or other sulfur sources to give L-cysteine 3,4 . OASS is a pyridoxal 5 0 -phosphate (PLP)-dependent enzyme that in bacteria is present in two isoforms, conventionally referred to as OASS-A and OASS-B, coded by cysK and cysM, respectively.…”

Section: Introductionmentioning

confidence: 99%

Cyclopropane-1,2-dicarboxylic acids as new tools for the biophysical investigation ofO-acetylserine sulfhydrylases by fluorimetric methods and saturation transfer difference (STD) NMR

Annunziato¹,

Pieroni²,

Benoni

et al. 2016

Journal of Enzyme Inhibition and Medicinal Chemistry

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Cysteine is a building block for many biomolecules that are crucial for living organisms. O-Acetylserine sulfhydrylase (OASS), present in bacteria and plants but absent in mammals, catalyzes the last step of cysteine biosynthesis. This enzyme has been deeply investigated because, beside the biosynthesis of cysteine, it exerts a series of ''moonlighting'' activities in bacteria. We have previously reported a series of molecules capable of inhibiting Salmonella typhimurium (S. typhymurium) OASS isoforms at nanomolar concentrations, using a combination of computational and spectroscopic approaches. The cyclopropane-1,2-dicarboxylic acids presented herein provide further insights into the binding mode of small molecules to OASS enzymes. Saturation transfer difference NMR (STD-NMR) was used to characterize the molecule/ enzyme interactions for both OASS-A and B. Most of the compounds induce a several fold increase in fluorescence emission of the pyridoxal 5 0 -phosphate (PLP) coenzyme upon binding to either OASS-A or OASS-B, making these compounds excellent tools for the development of competition-binding experiments.

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The multifaceted pyridoxal 5′-phosphate-dependent O-acetylserine sulfhydrylase

Cited by 42 publications

References 96 publications

Establishment of anIn Vitrod-Cycloserine-Synthesizing System by UsingO-Ureido-l-Serine Synthase andd-Cycloserine Synthetase Found in the Biosynthetic Pathway

Establishment of anIn Vitrod-Cycloserine-Synthesizing System by UsingO-Ureido-l-Serine Synthase andd-Cycloserine Synthetase Found in the Biosynthetic Pathway

Plant amino acid-derived vitamins: biosynthesis and function

Cyclopropane-1,2-dicarboxylic acids as new tools for the biophysical investigation ofO-acetylserine sulfhydrylases by fluorimetric methods and saturation transfer difference (STD) NMR

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