Dataset Information

Distinct Substrate Specificity and Catalytic Activity of the Pseudoglycosyltransferase VldE.

ABSTRACT: The pseudoglycosyltransferase (PsGT) VldE is a glycosyltransferase-like protein that is similar to trehalose 6-phosphate synthase (OtsA). However, in contrast to OtsA, which catalyzes condensation between UDP-glucose and glucose 6-phosphate, VldE couples two pseudosugars to give a product with an ?,?-N-pseudoglycosidic linkage. Despite their unique catalytic activity and important role in the biosynthesis of natural products, little is known about the molecular basis governing their substrate specificity and catalysis. Here, we report comparative biochemical and kinetic studies using recombinant OtsA, VldE, and their chimeric proteins with a variety of sugar and pseudosugar substrates. We found that the chimeric enzymes can produce hybrid pseudo-(amino)disaccharides, and an amino group in the acceptor is necessary to facilitate a coupling reaction with a pseudosugar donor. Furthermore, we found that the N-terminal domains of the enzymes not only play a major role in selecting the acceptors, but also control the type of nucleotidyl diphosphate moiety of the donors.

SUBMITTER: Abuelizz HA

PROVIDER: S-EPMC4475420 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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Distinct Substrate Specificity and Catalytic Activity of the Pseudoglycosyltransferase VldE.

Abuelizz Hatem A HA Mahmud Taifo T

Chemistry & biology 20150604 6

The pseudoglycosyltransferase (PsGT) VldE is a glycosyltransferase-like protein that is similar to trehalose 6-phosphate synthase (OtsA). However, in contrast to OtsA, which catalyzes condensation between UDP-glucose and glucose 6-phosphate, VldE couples two pseudosugars to give a product with an α,α-N-pseudoglycosidic linkage. Despite their unique catalytic activity and important role in the biosynthesis of natural products, little is known about the molecular basis governing their substrate sp ...[more]

PMID: 26051218

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Project description:Phospholipid oxidation generates several bioactive aldehydes that remain esterified to the glycerol backbone ('core' aldehydes). These aldehydes induce endothelial cells to produce monocyte chemotactic factors and enhance monocyte-endothelium adhesion. They also serve as ligands of scavenger receptors for the uptake of oxidized lipoproteins or apoptotic cells. The biochemical pathways involved in phospholipid aldehyde metabolism, however, remain largely unknown. In the present study, we have examined the efficacy of the three mammalian AKR (aldo-keto reductase) families in catalysing the reduction of phospholipid aldehydes. The model phospholipid aldehyde POVPC [1-palmitoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosphocholine] was efficiently reduced by members of the AKR1, but not by the AKR6 or the ARK7 family. In the AKR1 family, POVPC reductase activity was limited to AKR1A and B. No significant activity was observed with AKR1C enzymes. Among the active proteins, human AR (aldose reductase) (AKR1B1) showed the highest catalytic activity. The catalytic efficiency of human small intestinal AR (AKR1B10) was comparable with the murine AKR1B proteins 1B3 and 1B8. Among the murine proteins AKR1A4 and AKR1B7 showed appreciably lower catalytic activity as compared with 1B3 and 1B8. The human AKRs, 1B1 and 1B10, and the murine proteins, 1B3 and 1B8, also reduced C-7 and C-9 sn-2 aldehydes as well as POVPE [1-palmitoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosphoethanolamine]. AKR1A4, B1, B7 and B8 catalysed the reduction of aldehydes generated in oxidized C(16:0-20:4) phosphatidylcholine with acyl, plasmenyl or alkyl linkage at the sn-1 position or C(16:0-20:4) phosphatidylglycerol or phosphatidic acid. AKR1B1 displayed the highest activity with phosphatidic acids; AKR1A4 was more efficient with long-chain aldehydes such as 5-hydroxy-8-oxo-6-octenoyl derivatives, whereas AKR1B8 preferred phosphatidylglycerol. These results suggest that proteins of the AKR1A and B families are efficient phospholipid aldehyde reductases, with non-overlapping substrate specificity, and may be involved in tissue-specific metabolism of endogenous or dietary phospholipid aldehydes.

Dataset Information

Distinct Substrate Specificity and Catalytic Activity of the Pseudoglycosyltransferase VldE.

Publications

Distinct Substrate Specificity and Catalytic Activity of the Pseudoglycosyltransferase VldE.

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