Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.21 (beta-glucosidase)
 3,280 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glucocerebrosidase, the lysosomal enzyme that is deficient in patients with Gaucher's disease, hydrolyses non-physiological aryl beta-D-glucosides and glucocerebroside, its substrate in vivo. We document that 2,3,-di-O-tetradecyl-1-O-(beta-D-glucopyranosyl)-sn-glycerol (2,3,-di-14:0-beta-Glc-DAG) inhibits human placental glucocerebrosidase activity in vitro (Ki 0.18 mM), and the nature of inhibition is typical of a mixed-type pattern. Furthermore, 2,3-di-14:0-beta-Glc-DAG was shown to be an excellent substrate for the lysosomal beta-glucosidase (Km 0.15 mM; Vmax. 19.8 units/mg) when compared with the natural substrate glucocerebroside (Km 0.080 mM; Vmax. 10.4 units/mg). The observations that (i) glucocerebrosidase-catalysed hydrolysis of 2,3-di-14:0-beta-Glc-DAG is inhibited by conduritol B epoxide and glucosylsphingosine, and (ii) spleen and brain extracts from patients with Gaucher's disease are unable to hydrolyse 2,3-di-14:O-beta-Glc-DAG demonstrate that the same active site on the enzyme is responsible for catalysing the hydrolysis of 4-methylumbelliferyl beta-D-glucopyranoside, glucocerebroside and 2,3-di-14:O-beta-Glc-DAG. With the aid of computer modelling we have established that the oxygen atoms in 2,3-DAG-Glc at the C-1, C-4*, C-5* (the ring oxygen in glucose) and C-2 positions correspond topologically to the oxygens at C-1, C-4* and C-5* and the nitrogen atom attached to C-2 respectively in glucocerebroside (* signifies a carbon atom in glucose); furthermore, all of the distances with respect to overlap of corresponding heteroatoms range from 0.02 A to 0.77 A (0.002-0.077 nm). A root-mean-square deviation of 0.31 A (0.031 nm) was obtained when the energy-minimized structures of 2,3-di-14:O-beta-Glc-DAG and glucocerebroside were compared using the latter four heteroatom co-ordinates.
 ...
PMID:2,3-di-O-tetradecyl-1-O-(beta-D-glucopyranosyl)-sn-glycerol is a substrate for human glucocerebrosidase. 190 Sep 89

Trichoderma viride C-1 strain was irradiated with UV until the survival level of 0.03% was obtained. Sixteen mutants were isolated on the basis of the visible clearance zone around the colonies on the media with cellulose and glycerol. Then they were cultivated on a rotary shaker in the liquid Saunders medium supplemented with microcrystalline cellulose and comminuted sugar beet pulp. Exo-1,4-beta-glucanase, endo-1,4-beta-glucanase and beta-glucosidase were assayed in the supernatants of postcultural liquids at different time intervals of culture. The same mutants were characterized by higher biosynthesis level of exoglucanase (1.2-5.0 times) endoglucanase (1.2-2.5 times) and beta-glucosidase (1.5-1.7 times) when compared with the wild type strain.
 ...
PMID:The effect of Trichoderma viride C-1 UV mutagenization on cellulases activity. 262 84

Several beta-D-glucopyranosides (p-nitrophenyl, phenyl, and ethyl), 1-thio-beta-D-glucopyranosides, and phenyl 2-deoxy, 3-deoxy, 4-deoxy, and 6-deoxy beta-D-glucopyranosides were synthesized and used to study the mechanism of the enzymatic action of Taka-beta-glucosidase [EC 3.2.1.21 Aspergillus oryzae]. Kinetic constants of the enzyme for these glycosides were determined from S/V-S or 1/V-1/S plots, and the hydrolysis rates of these compounds with the enzyme, acid (3 N HCl) and alkali (3 N NaOH) were compared. Inhibition of the enzyme by 1,5-anhydroglucitol, glucal, dihydroglucal, and 1,6-anhydroglucopyranose was also examined. Glucal and 1,5-anhydroglucitol showed strong competitive inhibition. Free energy of binding of each hydroxyl group of glucosidic glucose with the enzyme was estimated from Kms of phenyl beta-glucoside and its deoxy analogues, and also Ki values of some inhibitors. The free energies of binding of 2-OH, 3-OH, 4-OH, and 6-OH were calculated to be 1.1, 2.4, 0.7, and 1.8 kcal/mol, respectively. The free energy of binding of phenoxide at C-1 (0.3 kcal/mol) was calculated from the Km of Ph-beta-Glc and Ki of 1,5-anhydroglucitol. The energy of binding of 5-CH2OH (2.3 kcal/mol) was obtained from the Km of Ph-beta-Glc and that of Ph-beta-Xyl. The sum (6.8 kcal/mol) of each partial binding free energy was close to the value of binding free energy of Ph-beta-Glc (7.0 kcal/mol) calculated by the equation; -delta Gbind = -RT ln Km-T delta Smix, showing that the methods of estimation of each binding energy used in the present study seemed reasonable. Glucal, having a pyranose form distorted slightly, showed strong competitive inhibition and the Ki of this inhibitor was smaller than the Km of Ph-beta-Glc, suggesting that the sugar ring bound to the active site was distored to a half chair form which is labile to acid hydrolysis.
 ...
PMID:Energy of binding of Aspergillus oryzae beta-glucosidase with the substrate, and the mechanism of its enzymic action. 641 35

The inhibition of four beta-glucosidases of plant, fungal, and mammalian origin by N1-butyl- and N1-dodecyl-D-gluconamidine was determined. Comparison with the inhibition by the corresponding N-alkyl-D-glucosylamines revealed that the strongly basic amidines (pKa 10.8) were at the most 10-times more inhibitory than the weakly basic glucosylamines (pKa 6.5). The small enhancement of inhibitory potency, resulting from transforming the tetrahedral C-1 geometry of the glucosylamines to the planar sp2-geometry of the amidines, was ascribed to the inability of the fully protonated amidines to function as hydrogen bond acceptors with the catalytic acid of the enzyme. Additional evidence for the importance of a hydrogen bond for strong inhibition came from the comparison of K1-values of the weakly basic 5-amino-5-deoxyhexopyranoses and 1,5-iminohexitols with those of the corresponding glyconamidrazones (pKa 8.4), which also have a planar C-1 geometry but are largely protonated under the assay conditions and which had similar or up to 10(4)-times larger K1-values than the former. Transition state resemblance was judged from the ratio KS(alkyl beta-glucoside)/K1(alkyl gluconamidine) relative to the rate acceleration factor kcat/kuncat (Wolfenden, Acc, Chem. Res., 5 (1972) 10-16). Compared to ratios of kcat/kuncat from > or = 10(11) to > or = 10(13), the ratios for KS/K1 were only from 10(3) to 2 x 10(4) except for beta-glucosidase A3 from Asp. wentii which had KS/K1 2.8 x 10(6). This enzyme differs from the others by being strongly inhibited by cationic glycon and substrate analogues rather than by basic ones. The pH-dependence of 1/K1 and the 'slow' approach to the inhibition is discussed with respect to transition state resemblance.
 ...
PMID:N1-alkyl-D-gluconamidines: are they 'perfect' mimics of the first transition state of glucosidase action? 887 Feb 40

Novel derivatives of the D-glucosidase inhibitor 2,5-dideoxy-2,5-imino-D-mannitol bearing lipophilic aliphatic or aromatic amides attached to C-1 have been found to inhibit beta-glucosidase from Agrobacterium sp. in the nanomolar range. One of them, a coumarin derivative, ranks amongst the most active compounds in the class of reversible glycosidase inhibitors of the iminoalditol type.
 ...
PMID:Novel, lipophilic derivatives of 2,5-dideoxy-2,5-imino-D-mannitol (DMDP) are powerful beta-glucosidase inhibitors. 1132 90

A range of new C-1 modified derivatives of the powerful glucosidase inhibitor 2,5-dideoxy-2,5-imino-D-mannitol has been synthesised and their biological activities probed with the beta-glucosidase from Agrobacterium sp. Ki values are compared with those of previously prepared close relatives. Findings suggest dramatic effects exerted by the aglycon binding site on substrate/inhibitor binding.
 ...
PMID:Probing the aglycon binding site of a beta-glucosidase: a collection of C-1-modified 2,5-dideoxy-2,5-imino-D-mannitol derivatives and their structure-activity relationships as competitive inhibitors. 1518 33

Glycosylation of the phenolic hydroxyl group of the phenyl propanoid systems, eugenol 1 and curcumin 2, using an amyloglucosidase from Rhizopus and a beta-glucosidase from sweet almonds together with carbohydrates (D-glucose 3, D-mannose 4, maltose 5, sucrose 6 and D-mannitol 7) in di-isopropyl ether produced glycosides at 7-52% yields in 72 h. Spectral studies indicated that the reaction occurred between the phenolic OH groups and C-1 and/or 6-O-groups of the carbohydrates with curcumin exhibiting bis glycosylation.
 ...
PMID:Amyloglucosidase-catalyzed synthesis of eugenyl and curcuminyl glycosides. 1721

In the search for an efficient producer of cellulolytic enzymes, Acremonium cellulolyticus strain C-1 was subjected to mutagenesis using UV-irradiation and N-methyl-N'nitro-N-nitrosoguanidine (NTG) and strain CF-2612 was isolated. Strain CF-2612 exhibited higher filter paperase (FPase) activities (17.8 U/ml) than the parent strain C-1 (12.3 U/ml). Soluble protein production and beta-glucosidase activity from strain CF-2612 were also significantly improved. FPase activity, cellulase productivity and yield of CF-2612 using batch culture with 5% Solka Floc in a 2-l jar fermentor at 30 degrees C reached 18.0 U/ml, 150.0 FPU/l/h and 360.0 FPU/g carbohydrate, respectively; when fed-batch culture was used with Solka Floc, these values reached 34.6 U/ml, 240.3 FPU/l/h and 346.0 FPU/g carbohydrate, respectively. It was observed that more hydrolyzed glucose was released from pretreated eucalyptus with the enzyme of strain CF-2612, compared with that of the commercial cellulase GC-220. This result was attributed to the higher ratio of beta-glucosidase/FPase activity of strain CF-2612. Three distinguishable phases including the periods of primary or second mycelial growth and mycelial fragmentation were proposed in batch culture by A. cellulolyticus.
 ...
PMID:Strain improvement of Acremonium cellulolyticus for cellulase production by mutation. 1926 88