On the inhibition of β-N-acetyl-D-glucosaminidase by 2-acetamido-2-deoxy-D-glucono-(1→5)-lactone

Leaback, David H.

doi:10.1016/0006-291x(68)90132-0

Cited by 73 publications

(23 citation statements)

References 9 publications

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“…[34] Levvy and Conchie later made the same observation with other glycosidases. [35±37] Leaback pointed to the ªstereochemical and conformational similarities between the lactone and the transition state in the enzyme-catalyzed pyranoside hydrolysisº, [38] and Reese et al [39] added that the polar oxy group also partially mimics the positive charge of the oxycarbenium ion intermediate 2 (Figure 1 b). The relative importance of these two features, shape and charge, [40] has remained the subject of much debate, much more so than their correlation with details of the enzymic mechanism.…”

Section: Shape or Charge?mentioning

confidence: 99%

Recent Insights into Inhibition, Structure, and Mechanism of Configuration-Retaining Glycosidases

Heightman

Vasella

1999

Angew. Chem. Int. Ed.

563

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Not "from above", but "from the side": Configuration-retaining β-glycosidases protonate their substrate either anti or syn to the endocyclic C1-O bond as the first step in the enzymic cleavage of the glycosidic bond (see schematic drawing). Insights into the mechanism of action of glycosidases have been gained by a combination of the synthesis of inhibitors, the study of the kinetics of their inhibition, and the analysis of the crystal structures of glycosidases and glycosidase-ligand complexes.

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Section: Shape or Charge?mentioning

confidence: 99%

Recent Insights into Inhibition, Structure, and Mechanism of Configuration-Retaining Glycosidases

Heightman

Vasella

1999

Angew. Chem. Int. Ed.

563

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“…-~-Glucono-l,5-lactone (1) is a well-known competitive inhibitor of /I-glucosidases (EC 3.2.1.21) with K, values of about 10-4-10-5 M [l] [2]. According to X-ray analysis [3] [4] and 'H-NMR spectra (see Table I), 1 adopts both in the solid state and in aqueous solution (predominantly) a distorted half-chair conformation; thus, it has been considered a transition-state analogue for the enzymatic cleavage Of /3-D-glUCOpyranosides [ 5 ] . Table 1. '…”

mentioning

confidence: 99%

Inhibition of Emulsin by D‐Gluconhydroximo‐1,5‐lactone and Related Compounds

Beer

Vasella

1986

Helvetica Chimica Acta

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“…The inhibitory effect that we describe for P-glucono-␦-lactone toward P-␤-glucosidase from F. mortiferum is reminiscent of the inhibition of ␤-glucosidase(s) by glucono-␦-lactone (17,18,21,42). Indeed, it is from these latter studies, and from current concepts of ␤-glucosidase catalysis (20,40,41,50,51), that we can propose reasonable explanations for the P-glucono-␦-lactone-mediated inhibition of P-␤-glucosidase from F. mortiferum.…”

Section: Fig 5 Binding Of the Inhibitory [U-mentioning

confidence: 80%

Phospho-beta-glucosidase from Fusobacterium mortiferum: purification, cloning, and inactivation by 6-phosphoglucono-delta-lactone

et al. 1997

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6-Phosphoryl-␤-D-glucopyranosyl:6-phosphoglucohydrolase (P-␤-glucosidase, EC 3.2.1.86) has been purified from Fusobacterium mortiferum. Assays for enzyme activity and results from Western immunoblots showed that P-␤-glucosidase (M r , 53,000; pI, 4.5) was induced by growth of F. mortiferum on ␤-glucosides. The novel chromogenic and fluorogenic substrates, p-nitrophenyl-␤-D-glucopyranoside-6-phosphate (pNP␤Glc6P) and 4-methylumbelliferyl-␤-D-glucopyranoside-6-phosphate (4MU␤Glc6P), respectively, were used for the assay of P-␤-glucosidase activity. The enzyme hydrolyzed several P-␤-glucosides, including the isomeric disaccharide phosphates cellobiose-6-phosphate, gentiobiose-6-phosphate, sophorose-6-phosphate, and laminaribiose-6-phosphate, to yield glucose-6-phosphate and appropriate aglycons. The kinetic parameters for each substrate are reported. P-␤-glucosidase from F. mortiferum was inactivated by 6-phosphoglucono-␦-lactone (P-glucono-␦-lactone) derived via oxidation of glucose 6-phosphate. The pbgA gene that encodes P-␤-glucosidase from F. mortiferum has been cloned and sequenced. The first 42 residues deduced from the nucleotide sequence matched those determined for the N terminus by automated Edman degradation of the purified enzyme. From the predicted sequence of 466 amino acids, two catalytically important glutamyl residues have been identified. Comparative alignment of the amino acid sequences of P-␤-glucosidase from Escherichia coli and F. mortiferum indicates potential binding sites for the inhibitory P-glucono-␦-lactone to the enzyme from F. mortiferum.Fusobacteria are important human pathogens that collectively comprise a genus of the Bacteroidaceae family of microorganisms (14, 23). Most species of Fusobacteria rely upon amino acid fermentation to provide requisite energy for growth, but F. mortiferum has the additional capacity to utilize a wide variety of carbohydrates, including monosaccharides and ␣-and ␤-glucosides as fermentable energy sources. Our interest in the mechanisms of amino acid and sugar utilization by Fusobacteria stems from the fact that the end products of these metabolic pathways include lactic, acetic, propionic, and butyric acids. These organic acids are cytotoxic for epithelial and other tissue cells, and Fusobacteria are believed to be causative agents or a contributing factor in the etiology of oral and other diseases.Studies in our laboratory (30,31,45) provided the first evidence for the operation of the phosphoenolpyruvate-dependent sugar:phosphotransferase system (PEP:PTS) in Fusobacteria. Although discovered serendipitously by Saul Roseman and his colleagues in Escherichia coli (16,34), this multicomponent system (35) is now recognized as the primary mechanism for the simultaneous translocation and phosphorylation of sugars by bacteria from both gram-positive (11, 29, 43) and gram-negative (22, 28) genera. Catabolism of disaccharides that are accumulated by the PEP-PTS as phosphorylated derivatives requires the cleavage of these compounds by intracellular substrate-sp...

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On the inhibition of β-N-acetyl-D-glucosaminidase by 2-acetamido-2-deoxy-D-glucono-(1→5)-lactone

Cited by 73 publications

References 9 publications

Recent Insights into Inhibition, Structure, and Mechanism of Configuration-Retaining Glycosidases

Recent Insights into Inhibition, Structure, and Mechanism of Configuration-Retaining Glycosidases

Inhibition of Emulsin by D‐Gluconhydroximo‐1,5‐lactone and Related Compounds

Phospho-beta-glucosidase from Fusobacterium mortiferum: purification, cloning, and inactivation by 6-phosphoglucono-delta-lactone

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