Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.2.1.23 (beta-galactosidase)
 14,648 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The gene lacS coding for a beta-galactosidase (beta Gal; EC 3.2.1.23) has been cloned from the thermoacidophilic archaebacterium Sulfolobus solfataricus, strain MT-4. It encodes a polypeptide chain of 489 amino acids (aa) (56,764 Da) in good agreement with the value directly measured for the enzyme (60 +/- 2 kDa per subunit). The aa composition of the enzyme and, in particular, its peculiarly low cysteine content (one Cys per subunit) has been confirmed; at the same time, it has been observed that the very low G + C content of the S. solfataricus genome strongly influences the codon usage preferences in the lacS sequence. There appears to be no evident similarity between this and the Escherichia coli lacZ sequence, thus suggesting that the two enzymes have analogous function, but are not homologous. By comparison with the published sequences of archaebacterial promoters, terminators and ribosome-binding sites, potential regulatory sites have been identified in the flanking regions of the S. solfataricus lacS gene.
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PMID:Isolation and sequencing of a new beta-galactosidase-encoding archaebacterial gene. 212 22

The conformations of nitrogen-in-the-ring sugars and their N-alkyl derivatives were studied from 1H NMR analyses, mainly using 3J(H,H) coupling constants and quantitative NOE experiments. No significant difference was seen in the ring conformation of 1-deoxynojirimycin (1), N-methyl-1-deoxynojirimycin (2), and N-butyl-1-deoxynojirimycin (3). However, it was shown that the C6 OH group in 1 is predominantly equatorial to the piperidine ring, while that in 2 or 3 is predominantly axial, and its N-alkyl group is oriented equatorially. In the furanose analogues 1,4-dideoxy-1,4-imino-D-arabinitol (4) and its N-methyl (5) and N-butyl (6) derivatives, the five-membered ring conformation differed significantly by the presence or absence of the N-substituted group and the length of the N-alkyl chain. Compound 3 reduced its inhibitory effect on almost all glycosidases, resulting in an extremely specific inhibitor for processing alpha-glucosidase I since N-alkylation of 1 is known to enhance both the potency and specificity of this enzyme in vitro and in vivo. This preferred (C6 OH axial) conformation in 2 and 3 appears to be responsible for their strong alpha-glucosidase I activity. Compound 4 is a good inhibitor of intestinal alpha-glucohydrolases, alpha-glucosidase II, and Golgi alpha-mannosidases I and II, but its N-alkyl derivatives 5 and 6 markedly decreased inhibitory potential for all enzymes tested. In the case of 2,5-dideoxy-2,5-imino-D-mannitol (DMDP, 7), which is a potent beta-galactosidase inhibitor, its N-methyl (8) and N-butyl (9) derivatives completely lost potency toward beta-galactosidase as well. N-Alkylation of compounds 4 and 7, known well as potent yeast alpha-glucosidase inhibitors, resulted in a serious loss of inhibitory activity toward yeast alpha-glucohydrolases. Activity of these nine analogues against HIV-1 replication was determined, based on the inhibition of virus-induced cytopathogenicity in MT-4 and MOLT-4 cells. Compounds 2 and 3, which are better inhibitors of alpha-glucosidase I than 1, proved active with EC50 values of 69 and 49 micrograms/mL in MT-4 cells and 100 and 37 micrograms/mL in MOLT-4 cells, respectively, while none of the furanose analogues exhibited any inhibitory effects on HIV-1. The change in potency and specificity of bioactivity by N-alkylation of nitrogen-in-the-ring sugars appears to be correlated with their conformational change.
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PMID:N-alkylated nitrogen-in-the-ring sugars: conformational basis of inhibition of glycosidases and HIV-1 replication. 760 1

The enzyme with beta-galactosidase activity from Sulfolobus solfataricus strain MT-4, like other enzymes of this type isolated from thermophilic sources, has broad specificity for beta-D-gluco-, fuco- and galacto-sides. The beta-galactosidase activity was purified by a new procedure that improved yields (44%) and final specific activity (182 units mg-1 at 75 degrees C using chromogenic beta-D-galactoside as substrate). The enzyme hydrolysed a large number of beta-linked glycoside dimers and oligomers; chromogenic beta-glucosides and beta-fucosides are the preferred substrates, and kinetic analysis indicated that they bind to a common catalytic site. The order of catalytic efficiency was beta 1-3 > beta 1-4 > beta 1-6 and cellotetraose > cellotriose > cellobiose for glucose dimers and oliogomers respectively. The cleavage occurred at the non-reducing end of the oligosaccharide, and the enzyme showed noticeable specificity also for the aglycone part of substrates. From these results the enzyme from S. solfataricus strain MT-4 is defined as a true glycosyl hydrolase with remarkable exo-glucosidase activity and it is designated S beta-gly.
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PMID:Exo-glucosidase activity and substrate specificity of the beta-glycosidase isolated from the extreme thermophile Sulfolobus solfataricus. 848 8

Sodium valproate (VPA), a simple branched-chain fatty acid that has anticonvulsant activity and is used in the treatment of many forms of epilepsy, has been reported to stimulate human immunodeficiency virus (HIV) type 1 replication in acutely infected CEM and chronically infected U1 cells (Chemico-Biological Interactions 1994;91:111-121). When attempting to reproduce and extend these findings, we confirmed that VPA is able to stimulate HIV-1(IIIB) replication in acutely infected CEM and C8166 T lymphocytic cell lines and chronically infected ACH-2 and U937/IIIB/LAI cells in a concentration-dependent manner. The stimulatory effect of VPA on HIV replication in CEM cells was not increased by pretreatment of the cells with VPA for 24 hr before infection. However, we could not detect any stimulatory effect of VPA on HIV-1(IIIB) replication in acutely infected peripheral blood mononuclear cells (PBMCs), MT-4, MT-2, HUT-78, and MOLT-4 (clone 8) cells and in chronically infected HUT-78/IIIB/LAI cells. The stimulatory effect by VPA under certain conditions (see above) may be ascribed to an enhanced HIV transcription, as VPA was found to enhance the HIV long terminal repeat (LTR)-directed expression of beta-galactosidase in transiently transfected HLtat, P4, and COS7 cells. VPA did not enhance beta-galactoside expression mediated by the cytomegalovirus (CMV) promoter. VPA did not affect HIV-induced syncytium formation. Nor had VPA any direct inactivating effect on HIV.
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PMID:Cell type-dependent effect of sodium valproate on human immunodeficiency virus type 1 replication in vitro. 900 4

Newly developed antiviral compounds consisting of an adamantane derivative chemically linked to a water-soluble polyanionic matrix were shown to inhibit HIV-1 infection in lymphoblastoid cells, HeLa CD4+ beta-galactosidase (MAGI) cells and macrophages. The effect of the compounds was recorded by measuring viral reverse transcriptase activity and p24 by ELISA in culture supernatant and by immunoblotting of cell lysates. In this paper we describe the data obtained with one of the most promising compounds, Amant. Amant was not toxic for the host cells at concentrations as high as 1 mg/ml. The inhibition of HIV-1 replication in MT-4 and MAGI cells was observed when Amant was added either before infection or with the virus (0 h of infection), and was expressed even when the compound added at 0 h was removed 1.5 h after infection. Its inhibitory concentration (IC50) against HIV-1 and HIV-2 replication was 2-6 and 93 microg/ml, respectively. The anti-HIV-1 effect of the compound was gradually decreased when it was added 1 and 2 h post infection, and no inhibition was observed when the compound was added 4 h after infection, suggesting that the compound as a membranotropic drug blocks an early step of replication. It completely prevented the transport of Gag proteins into the nuclei. Pretreatment of the virus with Amant did not reduce its infectious activity. The classical adamantane derivatives amantadine and rimantadine hydrochloride did not inhibit HIV replication.
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PMID:Inhibition of HIV-1 replication by newly developed adamantane-containing polyanionic agents. 1032 46