L-Aspartase from Escherichia coli: substrate specificity and role of divalent metal ions

Falzone, Christopher J.; Karsten, William E.; Conley, Judith D.; Viola, Ronald E.

doi:10.1021/bi00426a004

Cited by 60 publications

(42 citation statements)

References 26 publications

(29 reference statements)

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“…Brand and Lowenstein (1978) found K,IK, 0.16 for the enzyme from H. alvei, and Falzone et al (1988) calculated K, 0.66 mM for the enzyme from E. coli (the K, found in this study for DL-3-arsonoalanine was 0.7 mM and KJK, was 0.23). Since D-aspartic acid does not inhibit this enzyme (Falzone et al, 1988), the effect of the racemic 3-arsonoalanine we used was probably due to the L isomer. pable of exploitation.…”

Section: The Action Of Arsenical Analogues On Fumarate Hydratase and supporting

confidence: 54%

Synthesis of 3‐arsonoalanine and its action on aspartate aminotransferase and aspartate ammonia‐lyase

Ali

Dixon

1993

European Journal of Biochemistry

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) -EJB 93 0201/3 D~-3-Arsonoalanine has been synthesized by the Strecker synthesis from the unstable compound arsonoacetaldehyde. It inactivates pig heart cytosolic aspartate aminotransferase and inhibits aspartate ammonia-lyase by competing with aspartate (KJK,,, 0.23). The fumarate analogue (0-3-arsonoacrylic acid and the malate analogue (RS)-3-arsonolactate also inhibit fumarate hydratase, competing with fumarate (K,/K, 1.8) and malate (Ki/Km 1.6) respectively. Attempted non-enzymic transamination of 3-arsonoalanine gave elimination of arsenite, in contrast with the transamination of 3-phosphonoalanine, which is either successful or leads to loss of phosphate.Phosphonoalanine (2-amino-3-phosphonopropionic acid) occurs naturally (Horiguchi, 1984) and is biologically transaminated (Roberts et al., 1968). Its transamination product, phosphonopyruvate, is the first product in the biosynthesis of the carbon-phosphorus bond and is formed by isomerization of phosphoenolpyruvate (Seidel et al., 1988; Bowman et al., 1988). The present study describes the synthesis of the arsenical analogue of phosphoalanine. Since a 2-oxoalkylarsonic acid is unstable (Lacoste et al., 1992), any transamination of 3-arsonoalanine to arsonopyruvate might be followed by release of arsenate ; thus it might poison organisms that take it up. Kamal (1989) explored many synthetic routes that might lead to arsonoalanine, but it was only after Lacoste et al. (1992) showed that arsonoacetaldehyde, although unstable, could be made in solution by the action of periodate on 2,3-dihydroxypropylarsonic acid, that we could make arsonoalanine from this aldehyde by a Strecker synthesis. We therefore report its synthesis and some of its properties, as well as its elimination of arsenite on attempted transamination to arsonopyruvate.Since arsonoalanine is an analogue of aspartate, we have tested it on two enzymes that use aspartate as substrate: aspartate aminotransferase, which was slowly inactivated, and aspartate ammonia-lyase, which was inhibited competitively. As aspartate ammonia-lyase and fumarate hydratase (fumarase) catalyse analogous reactions involving reversible trans-elimination of water or ammonium from (S)-malate or L-aspartate, respectively, with the formation of fumarate (Scheme l), we also studied the action of the fumarate analogue (E)-3-arsonoacrylate and the malate analogue 3-arsonolactate (3-arsono-2-hydroxypropionic acid) on fumarate hydratase. They also proved to be competitive inhibitors.

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Section: The Action Of Arsenical Analogues On Fumarate Hydratase and supporting

confidence: 54%

Synthesis of 3‐arsonoalanine and its action on aspartate aminotransferase and aspartate ammonia‐lyase

Ali

Dixon

1993

European Journal of Biochemistry

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“…Further reactions in this cluster were connected with fumarate reductase via fumarate. Aspartate ammonia-lyase was up-regulated, to process aspartate into fumarate during anaerobic growth on glucose [36,37]. The second cluster contained six up-regulated reactions which were connected by the metabolite S -adenosyl-L-methionine.…”

Section: Resultsmentioning

confidence: 99%

Using gene expression data and network topology to detect substantial pathways, clusters and switches during oxygen deprivation of Escherichia coli

et al. 2007

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Background: Biochemical investigations over the last decades have elucidated an increasingly complete image of the cellular metabolism. To derive a systems view for the regulation of the metabolism when cells adapt to environmental changes, whole genome gene expression profiles can be analysed. Moreover, utilising a network topology based on gene relationships may facilitate interpreting this vast amount of information, and extracting significant patterns within the networks.

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“…However, this strategy is limited by the narrow substrate range and strict regioselectivity (preference for ammonia addition to the a-position) of ammonia lyases. [9,10] Phenylalanine aminomutase (PAM) from Taxus chinensis is a recently discovered enzyme that catalyses the conversion of aphenylalanine to b-phenylalanine; this is the first committed step in the biosynthesis of the N-benzoyl phenylisoserinoyl side-chain of the anticancer drug taxol. [11] Unlike the aminomutases that require external cofactors, [12] PAM relies on a protein-derived cofactor, 5-methylene-3,5-dihydroimidazol-4-one (MIO), which is formed autocatalytically in the active site from the internal tripeptide Ala-Ser-Gly.…”

Section: Introductionmentioning

confidence: 99%

Enzymatic Synthesis of Enantiopure α‐ and β‐Amino Acids by Phenylalanine Aminomutase‐Catalysed Amination of Cinnamic Acid Derivatives

Szymański

Wietzes

et al. 2009

ChemBioChem

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The phenylalanine aminomutase (PAM) from Taxus chinensis catalyses the conversion of alpha-phenylalanine to beta-phenylalanine, an important step in the biosynthesis of the N-benzoyl phenylisoserinoyl side-chain of the anticancer drug taxol. Mechanistic studies on PAM have suggested that (E)-cinnamic acid is an intermediate in the mutase reaction and that it can be released from the enzyme's active site. Here we describe a novel synthetic strategy that is based on the finding that ring-substituted (E)-cinnamic acids can serve as a substrate in PAM-catalysed ammonia addition reactions for the biocatalytic production of several important beta-amino acids. The enzyme has a broad substrate range and a high enantioselectivity with cinnamic acid derivatives; this allows the synthesis of several non-natural aromatic alpha- and beta-amino acids in excellent enantiomeric excess (ee >99 %). The internal 5-methylene-3,5-dihydroimidazol-4-one (MIO) cofactor is essential for the PAM-catalysed amination reactions. The regioselectivity of amination reactions was influenced by the nature of the ring substituent.

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L-Aspartase from Escherichia coli: substrate specificity and role of divalent metal ions

Cited by 60 publications

References 26 publications

Synthesis of 3‐arsonoalanine and its action on aspartate aminotransferase and aspartate ammonia‐lyase

Synthesis of 3‐arsonoalanine and its action on aspartate aminotransferase and aspartate ammonia‐lyase

Using gene expression data and network topology to detect substantial pathways, clusters and switches during oxygen deprivation of Escherichia coli

Enzymatic Synthesis of Enantiopure α‐ and β‐Amino Acids by Phenylalanine Aminomutase‐Catalysed Amination of Cinnamic Acid Derivatives

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