Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An enzyme-linked immunoabsorbent assay was developed to quantify the lectin present in the hemolymph of the freshwater prawn Macrobrachium rosenbergii. This method involves the use of murine monoclonal IgG1 with kappa light chain (designated as 3G1) antibodies raised against the purified lectin, the assay that we developed recognized as little as 30 ng/ml of lectin, and was used to measure the lectin concentration in animals at different maturation stages. The highest concentration of lectin was identified in the hemolymph from post-larval prawns and the lowest in molt stage adult animals. The hemagglutination activity of the lectin was four-fold higher in adult than in juvenile specimens, although in all cases N-acetylated sugar residues, such as N-acetyl-D-glucosamine, N-acetyl-D-galactosamine, and N-acetyl-D-neuraminic acid were inhibitors of the lectin activity, suggesting that lectin plays a role in the transport of N-acetylated sugar in juvenile prawns. Our results indicate that lectin concentration and hemagglutinating activity could be influenced by developmental conditions of the freshwater prawn.
Comp Biochem Physiol B Biochem Mol Biol 2000 Oct
PMID:Quantification of lectin in freshwater prawn (Macrobrachium rosenbergii ) hemolymph by ELISA. 1107 70

Ustilago maydis is an edible parasitic basidiomycete, which specifically infects corn (Zea mays) and teocintle (Z. diploperennis). To characterise the interaction between the basidiomycete and its host organism, we tested the effect of plant lectins with well-known sugar specificity on the growth and germination of U. maydis spores. Lectins specific for N-acetyl-D-galactosamine, such as those from Dolichos biflorus and Phaseolus lunatus, and the wheatgerm agglutinin specific for N-acetyl-D-glucosamine inhibited spore germination, but were ineffective in modifying U. maydis cell growth. The galactose-specific lectin from the corn coleoptyle inhibited both germination and cell growth, while the lectin concanavalin A (mannose/glucose specific) activated spore germination and growth. Our results suggest that specific saccharide-containing receptors participate in regulating the growth and maturation of U. maydis spores.
Cell Mol Life Sci 2000 Dec
PMID:Effect of plant lectins on Ustilago maydis in vitro. 1121 24

Cell adhesion molecules, some of which are lectins, play a key role in the control of normal and pathological processes of various living organisms. We found herein that N-acetyl-D-glucosamine-specific lectin, isolated from the ascidian Didemnum ternatanum (DTL), alters the growth properties of HeLa tumor cells depending on the anchorage. DTL was shown to increase the proliferation of HeLa cells grown in soft agar greatly (in anchorage-independent fashion). In contrast, DTL inhibits the proliferative activity of HeLa cells grown on solid substrate and acts as inductor of differentiation, slowing cell growth, increasing the cell attachment and spreading. Scanning electron microscopic data have demonstrated that DTL treatment resulted in pronounced changes of the shape and surface of HeLa cells. Changes of cellular morphology correlated with essential redistribution of actin microfilaments.
Mol Cell Biochem 2001 May
PMID:Effect of lectin from the ascidian on the growth and the adhesion of HeLa cells. 1150 76

We have investigated the regulation by N-acetyl-glucosamine of the nag1 gene of the mycoparasitic biocontrol fungus Trichoderma atroviride (= T. harzianum P1), which encodes a 73-kDa N-acetyl-beta-D-glucosaminidase. The use of translational fusions revealed that a 290-bp fragment of the 5' regulatory region of nag1 is sufficient to confer inducibility on the Aspergillus niger goxA gene. The region between positions -150 and -290, upstream of the nag1 coding region, was investigated using in vivo methylation protection analysis and electrophoretic mobility shift assays (EMSAs). Two neighbouring regions that interacted with regulatory proteins were identified, and bases essential for these interactions were determined in vitro. These data reveal protein binding to a CCCCT element at -240, a CCAGN(13)CTGG motif at -284, and a CCAAT-box which is present in the spacer of the latter motif. Evidence for the binding of a Hap2/3/5 complex to this CCAAT motif is presented. Protein binding to all three motifs was constitutive, and no differences were observed between induced and non-induced cultures. Mutation of either the CCAGN(13)CTGG or the AGGGG motif resulted in loss of inducibility of nag1 expression by N-acetyl-D-glucosamine in vivo.
Mol Genet Genomics 2002 Apr
PMID:Identification of the N-acetyl-D-glucosamine-inducible element in the promoter of the Trichoderma atroviride nag1 gene encoding N-acetyl-glucosaminidase. 1197 59

A mutant lysozyme in which Arg14 and His15 were deleted together exhibited higher activity toward glycol chitin than the wild-type lysozyme. Moreover, the mutant lysozyme, which is less stable than the wild-type lysozyme by 7 degrees C, showed a shift of temperature dependence of activity to the low temperature side compared with the wild-type lysozyme [Protein Eng. 7, 743-748 (1994)]. In the free enzyme, the internal motion of the mutant lysozyme was similar to that of the wild-type. The internal motions of the wild-type and mutant lysozymes in the enzyme-substrate complex increased more than those in the free enzymes. Moreover, the increased internal motions of the substrate-complexed mutant lysozyme were greater than those of the substrate-complexed wild-type lysozyme in several residues [J. Mol. Biol. 286, 1547-1565 (1999)]. The structure of the mutant lysozyme was very similar to that of the wild-type lysozyme. Both structures were also alike in the complex of the trimer of N-acetyl-D-glucosamine. The mobility from B-factors agreed to some degree with that from order parameters in the regions showing great mobility of the protein, but this was not the case in the regions showing fast motion. However, we came to the same conclusion that the increased activity of the mutant lysozyme is due to the increase in the fluctuation of the lysozyme molecule. B-factor and order parameter do not always exhibit harmony because the time-scale of the analysis of mobility is different. However, they are not incompatible but complementary for detecting precise protein motions.
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PMID:Fluctuations in free or substrate-complexed lysozyme and a mutant of it detected on x-ray crystallography and comparison with those detected on NMR. 1198 77

In humans, two major beta-hexosaminidase isoenzymes exist: Hex A and Hex B. Hex A is a heterodimer of subunits alpha and beta (60% identity), whereas Hex B is a homodimer of beta-subunits. Interest in human beta-hexosaminidase stems from its association with Tay-Sachs and Sandhoff disease; these are prototypical lysosomal storage disorders resulting from the abnormal accumulation of G(M2)-ganglioside (G(M2)). Hex A degrades G(M2) by removing a terminal N-acetyl-D-galactosamine (beta-GalNAc) residue, and this activity requires the G(M2)-activator, a protein which solubilizes the ganglioside for presentation to Hex A. We present here the crystal structure of human Hex B, alone (2.4A) and in complex with the mechanistic inhibitors GalNAc-isofagomine (2.2A) or NAG-thiazoline (2.5A). From these, and the known X-ray structure of the G(M2)-activator, we have modeled Hex A in complex with the activator and ganglioside. Together, our crystallographic and modeling data demonstrate how alpha and beta-subunits dimerize to form either Hex A or Hex B, how these isoenzymes hydrolyze diverse substrates, and how many documented point mutations cause Sandhoff disease (beta-subunit mutations) and Tay-Sachs disease (alpha-subunit mutations).
J Mol Biol 2003 Apr 11
PMID:Crystal structure of human beta-hexosaminidase B: understanding the molecular basis of Sandhoff and Tay-Sachs disease. 1266 33

The macrolide antibiotics are bacteriostatic agents interfering with protein synthesis but they are taken up by phagocytic cells, e.g. macrophages, neutrophils and fibroblasts which take up infectious organisms into phagosome-lysosomal vaculoes. Recent studies have suggested that these macrolide antibiotics block the spread of infections by mechanisms associated with the inflammation process. Herein is a study with clarithromycin using human THP-1 monocytes, a phagocytic cell which has not been studied to date. Clarithromycin was rapidly taken up by the monocytes (approximately 1%) utilizing both saturable carrier and passive processes at pH 7.4 but was exclusively passive at pH 6.8 and 5.0. The carrier process was energy and temperature dependent and appeared to be linked to certain ion channels. Efflux of the drug was rapid and complete in 1 hr. Intracellular disposition showed 74% in the cell sap and 11% in the nucleus. Upon stimulation with zymogen A or bacteria significant increases of uptake occurred in the isolated lysosome-phagosomes. Examination showed that initially clarithromycin treatment triggered the release of NO, H2O2, IL-1 and TNFalpha from the monocytes, known mediators of inflammation, but also mediators which cause bacterial cell death or apoptosis. The activity of the monocyte marker hydrolytic enzyme NAG was elevated at this time as well as protein kinase C activity. Treatment from 2-4 hr with clarithromycin appeared to reverse this process in that the chemical mediator release was reduced along with the activities of hydrolytic enzymes, e.g. NAG and cathepsin D with no evidence of lipid peroxidation and protective SOD enzyme activity elevation. The latter effects of the antibiotic would be useful in blocking the spread of infection or inflammation from the original site. The normal bacterial static killing effects of clarithromycin was evident at 24 but not 2 hr in both extracellular free bacteria and those bacteria phagocytosed by the THP-1 monocytes.
Res Commun Mol Pathol Pharmacol 2001
PMID:Disposition and functions of clarithromycin in human THP-1 monocytes during stimulated and unstimulated conditions. 1276 Apr 88

GafD in Escherichia coli G (F17) fimbriae is associated with diarrheal disease, and the structure of the ligand-binding domain, GafD1-178, has been determined at 1.7A resolution in the presence of the receptor sugar N-acetyl-D-glucosamine. The overall fold is a beta-barrel jelly-roll fold. The ligand-binding site was identified and localized to the side of the molecule. Receptor binding is mediated by side-chain as well main-chain interactions. Ala43-Asn44, Ser116-Thr117 form the sugar acetamide specificity pocket, while Asp88 confers tight binding and Trp109 appears to position the ligand. There is a disulfide bond that rigidifies the acetamide specificity pocket. The three fimbrial lectins, GafD, FimH and PapG share similar beta-barrel folds but display different ligand-binding regions and disulfide-bond patterns. We suggest an evolutionary path for the evolution of the very diverse fimbrial lectins from a common ancestral fold.
J Mol Biol 2003 Aug 22
PMID:The structural basis of receptor-binding by Escherichia coli associated with diarrhea and septicemia. 1290 17

Understanding the mechanisms of the interaction between a protein surface and its outer molecular environment is of primary relevance for the rational design of new drugs and engineered proteins. Protein surface accessibility is emerging as a new dimension of Structural Biology, since NMR methods have been developed to follow how molecules, even those different from physiological ligands, preferentially approach specific regions of the protein surface. Hen egg-white lysozyme, a paradigmatic example of the state of the art of protein structure and dynamics, has been selected as a model system to study protein surface accessibility. Bound water and soluble spin-labels have been used to investigate the interaction of this enzyme, both free and bound to the inhibitor (NAG)(3), with its molecular environment. No tightly bound water molecules were found inside the enzyme active site, which, conversely, appeared as the most exposed to visits from the soluble paramagnetic probe TEMPOL. From the presented set of data, an integrated view of lysozyme surface accessibility towards water and TEMPOL molecules is obtained.
J Mol Biol 2003 Sep 12
PMID:NMR studies of protein hydration and TEMPOL accessibility. 1294 93

Mannose-binding lectin (MBL) is a pattern recognition molecule of the innate immune system. It belongs to the collectin family of proteins in which lectin (carbohydrate-recognition) domains are found in association with collagenous structures. In man, these proteins include serum MBL, lung surfactant protein A (SP-A) and lung surfactant protein D (SP-D). MBL binds to a range of sugars including N-acetyl-D-glucosamine, mannose, N-acetyl-mannosamine, fucose and glucose. This permits the protein to interact with a wide selection of viruses, bacteria, yeasts, fungi and protozoa decorated with such sugars. Unlike the other collectins, MBL bound to microbial surfaces is able to activate the complement system in an antibody and C1-independent manner. This activation is mediated by complexes of MBL with a serine protease called MBL-associated serine protease 2 (MASP-2), which specifically cleaves C4 and C2 to create a C3 convertase enzyme. MBL may also interact directly with cell surface receptors and thereby promote opsonophagocytosis by a complement-independent pathway. It has been suggested that MBL plays an important role in the first hours/days of any primary immune response to a sugar decorated pathogen. This provides the host with a first-line of defence before the adaptive immune system becomes operative and in humans may be particularly important between 6 and 18 months of age when the adaptive system is still immature. MBL deficiency is one of the most common human immunodeficiencies and arises primarily from three single point mutations in exon 1 of the MBL-2 gene. These mutations result in a failure to assemble fully functional multimeric protein. Several studies have shown that deficiency of MBL increases the overall susceptibility of an individual to infectious disease. The most striking example of this is the association of acute respiratory tract infections with MBL deficiency in early childhood. In contrast, there is evidence that for some intracellular parasites MBL deficiency may be protective and this might explain the high frequency of MBL mutations in sub-Saharan Africa and South America. Increasingly, there is evidence that the association between MBL levels and disease is complex. For example, the protein appears to influence the severity of several diseases. The mechanism whereby MBL exerts such effects is unclear but one possibility is through a dose-dependent modulation of pro-inflammatory cytokines.
Mol Immunol 2003 Nov
PMID:The role of mannose-binding lectin in health and disease. 1456 88


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