Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.2.1.20 (alpha-glucosidase)
 4,237 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The alpha-glucosidase inhibitor acarbose is modified during incubation with cell-free extract from the producing Actinoplanes strain. The formation of this product depends on the presence of ATP. Chromatographic and chemical properties of the purified transformation product indicate the presence of a phosphate ester. The structure is deduced by NMR analysis and shown to be acarbose-7-phosphate.
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PMID:Formation of acarbose phosphate by a cell-free extract from the acarbose producer Actinoplanes sp. 878 26

A phosphotransferase which modifies the alpha-glucosidase inhibitor acarbose by phosphorylation at its 7-position was isolated from the acarbose producer Actinoplanes sp. and purified to homogeneity. The sequence of the first 20 amino acids of the enzyme was determined. The enzyme is an ATP-dependent kinase and shows high specificity for acarbose and some related compounds containing the pseudodisaccharide moiety (acarviosin). The product formed by the enzyme, acarbose-7-phosphate, shows a significant lower inhibitory activity towards disaccharidases than acarbose itself. The acarbose producing organism contains a maltase which is inhibited by acarbose, but to a much lesser extent by acarbose-7-phosphate. The possible role of acarbose 7-phospho-transferase as part of a self-defense mechanism against acarbose in the producing organism is discussed.
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PMID:Acarbose 7-phosphotransferase from Actinoplanes sp.: purification, properties, and possible physiological function. 878 28

An apyrase and an alpha-glucosidase were detected in the salivary glands extracts of adult Aedes albopictus. The apyrase is a 61,000 Da secreted protein that hydrolyses ATP and ADP. This protein is synthe-sized in adults and is preferentially accumulated in the distal lateral lobes of the female salivary glands. The alpha-glucosidase is a secreted 67,000 Da protein. This enzyme is synthesized during adult life and accumulated in the proximal-lateral lobes of both males and females. The results are discussed and compared with data previously obtained with Aedes aegypti salivary glands.
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PMID:Apyrase and alpha-glucosidase in the salivary glands of Aedes albopictus. 892 36

The groEL gene of the alkaliphilic Bacillus sp. strain C-125 was cloned in Escherichia coli and sequenced. The groEL gene encoded a polypeptide of 544 amino acids and was preceded by the incomplete groES gene, lacking its 5'-end. The sequence of the derived amino acids was 87.5% identical to that of B. subtilis, 85.4% identical to that of B. stearothemophilus, and 60.9% identical to that of E. coli. The GroEL protein was expressed in E. coli. Purified GroEL protected yeast alpha-glucosidase from irreversible aggregation at a high temperature and the addition of Mg-ATP was essential for reactivation of the alpha-glucosidase. The addition of E. coli GroES increased recovery of the enzyme activity, indicating that C-125 GroEL could function in coordination with E. coli GroES.
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PMID:Molecular cloning and nucleotide sequence of the groEL gene from the alkaliphilic Bacillus sp. strain C-125 and reactivation of thermally inactivated alpha-glucosidase by recombinant GroEL. 898 60

We have purified to apparent homogeneity and characterized a molecular chaperonin GroEL homologue (hpGroEL) from a moderately halophilic eubacterium, Pseudomonas sp. #43. Although this halophilic bacterium requires 1-2 M NaCl for growth, hpGroEL did not require a high concentration of salt for its stability, ATPase activity and refold-promoting activity for denatured protein. The ATPase activity was even more halo-sensitive than that of GroEL from Escherichia coli. The hpGroEL protein promotes Mg(2+)-ATP-dependent refolding of urea-denatured alpha-glucosidase in the presence of E. coli-GroES, indicating that chaperonins 60 and 10 isolated from halophilic and nonhalophilic eubacteria, respectively, can cooperate with each other.
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PMID:Purification and characterization of a GroEL homologue from the moderately eubacterial halophile Pseudomonas sp. #43. 923 26

We have studied the uptake of maltose in the thermoacidophilic gram-positive bacterium Alicyclobacillus acidocaldarius, which grows best at 57 degrees C and pH 3.5. Under these conditions, accumulation of [(14)C]maltose was observed in cells grown with maltose but not in those grown with glucose. At lower temperatures or higher pH values, the transport rates substantially decreased. Uptake of radiolabeled maltose was inhibited by maltotetraose, acarbose, and cyclodextrins but not by lactose, sucrose, or trehalose. The kinetic parameters (K(m) of 0.91 +/- 0.06 microM and V(max) ranging from 0.6 to 3.7 nmol/min/mg of protein) are consistent with a binding protein-dependent ATP binding cassette (ABC) transporter. A corresponding binding protein (MalE) that interacts with maltose with high affinity (K(d) of 1.5 microM) was purified from the culture supernatant of maltose-grown cells. Immunoelectron microscopy revealed distribution of the protein throughout the cell wall. The malE gene was cloned and sequenced. Five additional open reading frames, encoding components of a maltose transport system (MalF and MalG), a putative transcriptional regulator (MalR), a cyclodextrinase (CdaA), and an alpha-glucosidase (GlcA), were identified downstream of malE. The malE gene lacking the DNA sequence that encodes the signal sequence was expressed in Escherichia coli. The purified wild-type and recombinant proteins bind maltose with high affinity over a wide pH range (2.5 to 7) and up to 80 degrees C. Recombinant MalE cross-reacted with an antiserum raised against the wild-type protein, thereby indicating that the latter is the product of the malE gene. The MalE protein might be well suited as a model to study tolerance of proteins to low pH.
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PMID:Maltose and maltodextrin transport in the thermoacidophilic gram-positive bacterium Alicyclobacillus acidocaldarius is mediated by a high-affinity transport system that includes a maltose binding protein tolerant to low pH. 1105 72

Solute transport in Saccharomyces cerevisiae can be regulated through mechanisms such as trans-inhibition and/or catabolite inactivation by nitrogen or carbon sources. Studies in hybrid membranes of S. cerevisiae suggested that the maltose transport system Mal61p is fully reversible and capable of catalyzing both influx and efflux transport. This conclusion has now been confirmed by studies in a S. cerevisiae strain lacking the maltase enzyme. Whole cells of this strain, wherein the orientation of the maltose transporter is fully preserved, catalyze fully reversible maltose transport. Catabolite inactivation of the maltose transporter Mal61p was studied in the presence and absence of maltose metabolism and by the use of different glucose analogues. Catabolite inactivation of Mal61p could be triggered by maltose, provided the sugar was metabolized, and the rate of inactivation correlated with the rate of maltose influx. We also show that 2-deoxyglucose, unlike 6-deoxyglucose, can trigger catabolite inactivation of the maltose transporter. This suggests a role for early glycolytic intermediates in catabolite inactivation of the Mal61 protein. However, there was no correlation between intracellular glucose-6-phosphate or ATP levels and the rate of catabolite inactivation of Mal61p. On the basis of their identification in cell extracts, we speculate that (dideoxy)-trehalose and/or (deoxy)-trehalose-6-phosphate trigger catabolite inactivation of the maltose transporter.
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PMID:Regulation of maltose transport in Saccharomyces cerevisiae. 1147 8

The anti-diabetic drug miglitol, an alpha-glucosidase inhibitor, which is currently used clinically, reduces myocardial infarct size by reducing the glycogenolytic rate through inhibition of the alpha-1,6-glucosidase of glycogen-debranching enzyme in the heart. Nicorandil, a K(ATP) channel opener with a nitrate-like effect, which is also currently used clinically, also reduces the infarct size. Therefore, we hypothesized that combination of nicorandil and submaximal dose of miglitol could markedly reduce myocardial infarct size more than miglitol or nicorandil alone, and investigated the mechanism for the infarct size-reducing effect. Japanese white rabbits without collateral circulation were subjected to 30 min coronary occlusion followed by 48 h reperfusion. Pre-ischaemic treatment with submaximal dose of miglitol (5 mg kg(-1), i.v.) and nicorandil alone (100 microg kg(-1) min(-1) 5 min) moderately reduced the infarct size as a percentage of area at risk (24+/-4 and 25+/-4%, respectively), and 10 mg kg(-1) of miglitol markedly reduced the infarct size (15+/-2%) compared with the controls (42+/-2%). Combination of 5 mg kg(-1) of miglitol and nicorandil (100 microg kg(-1) min(-1) 5 min), and 10 mg kg(-1) of miglitol and nicorandil (100 microg kg(-1) min(-1) 5 min) significantly reduced the infarct size (13+/-4 and 12+/-3%, respectively) more than miglitol or nicorandil alone. Pretreatment with 5HD completely abolished the infarct size-reducing effect of 10 mg kg(-1) of miglitol alone (36+/-7%) and that of combination of 5 mg kg(-1) of miglitol and nicorandil (46+/-2%). Combination of nicorandil and submaximal dose of miglitol markedly reduced the myocardial infarct size more than miglitol or nicorandil alone. This effect was suggested to be related to the opening of mitochondrial K(ATP) channels.
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PMID:Combination of miglitol, an anti-diabetic drug, and nicorandil markedly reduces myocardial infarct size through opening the mitochondrial K(ATP) channels in rabbits. 1148 14

Glycogen debranching enzyme was partially purified from bovine brain using a substrate for measuring the amylo-1,6-glucosidase activity. Bovine cerebrum was homogenized, followed by cell-fractionation of the resulting homogenate. The enzyme activity was found mainly in the cytosolic fraction. The enzyme was purified 5,000-fold by ammonium sulfate precipitation, anion-exchange chromatography, gel-filtration, anion-exchange HPLC, and gel-permeation HPLC. The enzyme preparation had no alpha-glucosidase or alpha-amylase activities and degraded phosphorylase limit dextrin of glycogen with phosphorylase. The molecular weight of the enzyme was 190,000 and the optimal pH was 6.0. The brain enzyme differed from glycogen debranching enzyme of liver or muscle in its mode of action on dextrins with an alpha-1,6-glucosyl branch, indicating an amino acid sequence different from those of the latter two enzymes. It is likely that the enzyme is involved in the breakdown of brain glycogen in concert with phosphorylase as in the cases of liver and muscle, but that this proceeds in a somewhat different manner. The enzyme activity decreased in the presence of ATP, suggesting that the degradation of brain glycogen is controlled by the modification of the debranching enzyme activity as well as the phosphorylase.
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PMID:Glycogen debranching enzyme in bovine brain. 1153 24

We have previously demonstrated that the biosynthesis of the C(7)-cyclitol, called valienol (or valienamine), of the alpha-glucosidase inhibitor acarbose starts from the cyclization of sedo-heptulose 7-phosphate to 2-epi-5-epi-valiolone (Stratmann, A., Mahmud, T., Lee, S., Distler, J., Floss, H. G., and Piepersberg, W. (1999) J. Biol. Chem. 274, 10889-10896). Synthesis of the intermediate 2-epi-5-epi-valiolone is catalyzed by the cyclase AcbC encoded in the biosynthetic (acb) gene cluster of Actinoplanes sp. SE50/110. The acbC gene lies in a possible transcription unit, acbKLMNOC, cluster encompassing putative biosynthetic genes for cyclitol conversion. All genes were heterologously expressed in strains of Streptomyces lividans 66 strains 1326, TK23, and TK64. The AcbK protein was identified as the acarbose 7-kinase, which had been described earlier (Drepper, A., and Pape, H. (1996) J. Antibiot. (Tokyo) 49, 664-668). The multistep conversion of 2-epi-5-epi-valiolone to the final cyclitol moiety was studied by testing enzymatic mechanisms such as dehydration, reduction, epimerization, and phosphorylation. Thus, a phosphotransferase activity was identified modifying 2-epi-5-epi-valiolone by ATP-dependent phosphorylation. This activity could be attributed to the AcbM protein by verifying this activity in S. lividans strain TK64/pCW4123M, expressing His-tagged AcbM. The His-tagged AcbM protein was purified and subsequently characterized as a 2-epi-5-epi-valiolone 7-kinase, presumably catalyzing the first enzyme reaction in the biosynthetic route, leading to an activated form of the intermediate 1-epi-valienol. The AcbK protein could not catalyze the same reaction nor convert any of the other C(7)-cyclitol monomers tested. The 2-epi-5-epi-valiolone 7-phosphate was further converted by the AcbO protein to another isomeric and phosphorylated intermediate, which was likely to be the 2-epimer 5-epi-valiolone 7-phosphate. The products of both enzyme reactions were characterized by mass spectrometric methods. The product of the AcbM-catalyzed reaction, 2-epi-5-epi-valiolone 7-phosphate, was purified on a preparative scale and identified by NMR spectroscopy. A biosynthetic pathway for the pseudodisaccharidic acarviosyl moiety of acarbose is proposed on the basis of these data.
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PMID:Biosynthesis of the C(7)-cyclitol moiety of acarbose in Actinoplanes species SE50/110. 7-O-phosphorylation of the initial cyclitol precursor leads to proposal of a new biosynthetic pathway. 1193 12


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