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

1. A homologous series of beta-glcosidase (beta-D-glcoside glcohydrolase, EC 3.2.1.21), which varied in relative amounts in different preparations from cultures of similar and different age, was observed in cultures od Botryodiplodia theobromae Pat grown for 4-8 week on cotton flock (cellulose) as carbon source. 2. Aging of the purified high-molecular-weight species led to some amount of siddociation into a homolous series of lower-molecular-weight speices. 3. Rough molecular-weight estimates, by gel filtration, of the various species derived from the purifeid high-molecular-weight enzyme were 350000-3800000, 170000, 180000, 83000-87000 and 45000-47000. 4. Electron micrographs of the negatively stained 350000-380000-molecular-weight enzyme showed that the molecule is an octamer in which each roughly spherical monomer occupies a corner of a cube with each side about 7.14nm long. 5. Carboxamidomethylation of the reduced form of each molecular-weight species of the enzyme led to irreversible dissociation of the molecules into electrophoretically identical polypeptides with a moleclar weight of 10000-12000. 6. These results suggest a slow association-dissociation of the type (8n)in equilibrium 2 (4n) in equilibrium 4(2n) in equilibrium 8(n), where n is defined as the monomer. The monomer is in turn made up of four polypeptide a subunits whi-ch are non-catalytic. 7. The Michaelis constants (Km) and heat stability of the four wnzymically active molecular species derived from the purified enzyme increased with molecular complexity, whereas all four species were inhibited by glycerol (100nM) at low concentrations of substrate (o-nitrophenyl beta-D-glucopyranoside) but activated at high substrat concentrations. 8. Only the lowest-molecular-weight species (45species (45,000-47000 mol. wt.) showed substrate inhibition.
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PMID:The subunit structure of beta-glucosidase from Botryodiplodia theobromae Pat. 115 65

The nucleotide sequence of the Clostridium thermocellum gene licB, coding for a thermoactive beta-1,3-1,4-glucanase, has been determined. The gene is located downstream, but in opposite orientation to the beta-glucosidase gene bglA. A coding region of 1002 bp is flanked by canonical promoter and transcription terminator sequences. The primary translation product of the licB gene has a predicted molecular mass of 37,896 Da. The protein sequence can be divided into several discrete segments: an N-terminal signal peptide, a catalytic region, a segment rich in Pro and Thr residues and a C-terminal reiterated domain. The catalytic region shows close similarity to lichenases of bacilli (52-58% identity) and Fibrobacter succinogenes (35% identity), but is unrelated to barley beta-1,3-1,4-glucanases. It consists of two domains, which in the case of the F. succinogenes lichenase are arranged in reversed order to that of C. thermocellum and Bacillus lichenases. The C-terminal reiterated domain of C. thermocellum lichenase is homologous to the duplicated non-catalytic domain of endo-beta-1,4-glucanases and xylanase Z from the same organism. This domain is considered a characteristic feature of clostridial cellulases organized as multienzyme complex (cellulosome). The beta-1,3-1,4-glucanase encoded by the licB gene might therefore be an additional enzyme component of the C. thermocellum cellulosome.
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PMID:Structure of the Clostridium thermocellum gene licB and the encoded beta-1,3-1,4-glucanase. A catalytic region homologous to Bacillus lichenases joined to the reiterated domain of clostridial cellulases. 174 Jan 23

Gaucher disease, the most common lysosomal storage disease, is caused by mutations in the gene that encodes acid-beta-glucosidase (GlcCerase). Type 1 is characterized by hepatosplenomegaly, and types 2 and 3 by early or chronic onset of severe neurological symptoms. No clear correlation exists between the approximately 200 GlcCerase mutations and disease severity, although homozygosity for the common mutations N370S and L444P is associated with non- neuronopathic and neuronopathic disease, respectively. We report the X-ray structure of GlcCerase at 2.0 A resolution. The catalytic domain consists of a (beta/alpha)(8) TIM barrel, as expected for a member of the glucosidase hydrolase A clan. The distance between the catalytic residues E235 and E340 is consistent with a catalytic mechanism of retention. N370 is located on the longest alpha-helix (helix 7), which has several other mutations of residues that point into the TIM barrel. Helix 7 is at the interface between the TIM barrel and a separate immunoglobulin-like domain on which L444 is located, suggesting an important regulatory or structural role for this non-catalytic domain. The structure provides the possibility of engineering improved GlcCerase for enzyme-replacement therapy, and for designing structure-based drugs aimed at restoring the activity of defective GlcCerase.
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PMID:X-ray structure of human acid-beta-glucosidase, the defective enzyme in Gaucher disease. 1279 54

The assembly into supramolecular complexes of proteins having complementary activities is central to cellular function. One such complex of considerable biological and industrial significance is the plant cell wall-degrading apparatus of anaerobic microorganisms, termed the cellulosome. A central feature of bacterial cellulosomes is a large non-catalytic protein, the scaffoldin, which contains multiple cohesin domains. An array of digestive enzymes is incorporated into the cellulosome through the interaction of the dockerin domains, present in the catalytic subunits, with the cohesin domains that are present in the scaffoldin. By contrast, in anaerobic fungi, such as Piromyces equi, the dockerins of cellulosomal enzymes are often present in tandem copies; however, the identity of the cognate cohesin domains in these organisms is unclear, hindering further biotechnological development of the fungal cellulosome. Here, we characterise the solution structure and function of a double-dockerin construct from the P. equi endoglucanase Cel45A. We show that the two domains are connected by a flexible linker that is short enough to keep the binding sites of the two domains on adjacent surfaces, and allows the double-dockerin construct to bind more tightly to cellulosomes than a single domain and with greater coverage. The double dockerin binds to the GH3 beta-glucosidase component of the fungal cellulosome, which is thereby identified as a potential scaffoldin.
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PMID:Characterization of a double dockerin from the cellulosome of the anaerobic fungus Piromyces equi. 1786 67

The complete degradation of cellulose to glucose is essential to carbon turnover in terrestrial ecosystems and to engineered biofuel production. A rate-limiting step in this pathway is catalyzed by beta-glucosidase (BG) enzymes, which convert cellulobiose into two glucose molecules. The activity of these enzymes has been shown to vary with solution pH. However, it is not well understood how pH influences the enzyme conformation required for catalytic action on the substrate. A structural understanding of this pH effect is important for predicting shifts in BG activity in bioreactors and environmental matrices, in addition to informing targeted protein engineering. Here we applied molecular dynamics simulations to explore conformational and substrate binding dynamics in two well-characterized BGs of bacterial (Clostridium cellulovorans) and fungal (Trichoderma reesei) origins as a function of pH. The enzymes were simulated in an explicit solvated environment, with NaCl as electrolytes, at their prominent ionization states obtained at pH 5, 6, 7, and 7.5. Our findings indicated that pH-dependent changes in the ionization states of non-catalytic residues localized outside of the immediate active site led to pH-dependent disruption of the active site conformation. This disruption interferes with favorable H-bonding interactions with catalytic residues required to initiate catalysis on the substrate. We also identified specific non-catalytic residues that are involved in stabilizing the substrate at the optimal pH for enzyme activity. The simulations further revealed the dynamics of water-bridging interactions both outside and inside the substrate binding cleft during structural changes in the enzyme-substrate complex. These findings provide new structural insights into the pH-dependent substrate binding specificity in BGs.
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PMID:Short-time dynamics of pH-dependent conformation and substrate binding in the active site of beta-glucosidases: A computational study. 2616 Jul 37

The effect of non-catalytic protein addition on the adsorption/desorption behavior of individual cellulase components on/from substrates during the hydrolysis of microcrystalline cellulose and steam exploded sugarcane bagasse (SEB) were investigated. The addition of non-catalytic protein enhanced the enzymatic hydrolysis of SEB, but did not enhance the hydrolysis of microcrystalline cellulose. During the hydrolysis of SEB, adsorption of beta-glucosidase (BGL) was prevented in the presence of non-catalytic protein. Cellobiohydrolase I (CBH I) and endoglucanase I (EG I) desorbed from the substrate after temporary adsorption in the presence of non-catalytic protein during SEB hydrolysis. This suggested that reduction of the non-specific adsorption of cellulase components, CBH I, EG I, and BGL, on lignin in SEB led to the improving of enzymatic hydrolysis.
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PMID:Quantitative analysis of adsorption and desorption behavior of individual cellulase components during the hydrolysis of lignocellulosic biomass with the addition of lysozyme. 2831 63