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Query: UNIPROT:P06889 (Mol)
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Two high molecular weight cuticular proteins (MSCP120 and MSCP246) were extracted in acidic guanidine hydrochloride solution from tanning abdominal cuticle of Manduca sexta pharate pupae and purified by size exclusion high performance liquid chromatography. The apparent molecular weights were ca. 120 and 246 kDa as determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis. Both proteins contained high levels of glutamate/glutamine, glycine, serine, alanine and aspartate/asparagine. MSCP120 was enriched in histidine relative to MSCP246, but the reverse was true for valine and proline. Small quantities of beta-alanine and 3,4-dihydroxyphenylalanine (DOPA), as well as other catechols and carbohydrates, also were detected in the hydrolysates. The proteins became radiolabeled when [1-14C]-beta-alanine was injected into pharate pupae, presumably by the formation of adducts with N-beta-alanyldopamine metabolites during sclerotization. Mild acid hydrolysis released N-beta-alanylnorepinephrine and 3,4-dihydroxyphenylketoethanol from both proteins. Strong acid hydrolysis yielded predominantly 3,4-dihydroxyphenylketoethylamine (arterenone), but also DOPA and dopamine. The N-terminal amino acid sequences of the two cuticular proteins were dissimilar, and that of MSCP246 was more hydrophobic than MSCP120. Both of these proteins were glycosylated with glucose, N-acetylglucosamine and traces of N-acetylgalactosamine, and MSCP246 also contained galactose. These structural glycoproteins, which occur in cuticle undergoing sclerotization, apparently react post-translationally with quinonoid tanning agents to yield catecholamine-protein adducts. Small amounts of peptidyl DOPA probably are formed by hydroxylation of tyrosyl residues. Results from this study are consistent with the hypothesis that these catechol-containing glycoproteins participate in cross-linking reactions in M. sexta pupal cuticle during sclerotization.
Insect Biochem Mol Biol 1994 Sep
PMID:Characterization of two high molecular weight catechol-containing glycoproteins from pharate pupal cuticle of the tobacco hornworm, Manduca sexta. 798 28

Hamster submaxillary glycoprotein (HSM), one of the simplest glycoproteins among mammalian salivary mucins, is composed of approximately equivalent amounts of protein, hexosamine and sialic acid. The Thr and Ser residues in the protein core account for more than half of all of the amino acid residues, while Lys, Glu, Pro and Ala are the major components of the remaining portion of amino acids. The carbohydrate side chains of this mucous glycoprotein have mainly the NeuAc-GalNAc-(sialyl-Tn) sequence (HSM), and those of the desialylated product (HSM-Tn) are almost exclusively unsubstituted GalNAc residues (Tn determinants). The binding properties of sialyl-Tn (HSM) and asialo-HSM (HSM-Tn) glycoproteins were tested by precipitin assay with Gal, GalNAc and GlcNAc specific lectins. The HSM-Tn completely precipitated Vicia villosa (VVL both B4 and mixture of A and B), Maclura pomifera (MPL), and Artocarpus integrifolia (Jacalin) lectins; less than 2 micrograms of HSM-Tn were required for precipitating 50% of 5.0-6.3 micrograms lectin nitrogen added. HSM-Tn also reacted well with Helix pomatia lectin (HPL), Wistaria floribunda lectin (WFL) and Abrus precatorius agglutinin (APA) and precipitated in each case over 81% of the lectin nitrogen added. The reactivity of HSM-Tn with other lectins (Ricinus communis, RCA1; Dolichol biflorus, DBL; Viscum album, ML-I; Arachis hypogaea, PNA, and Triticum vulgaris, WGA) was weak or negligible. The activity of sialyl-Tn (HSM) was more restricted; HSM reacted well with Jacalin, moderately with MPL and VVL-B4, but was inactive or only weakly with the other lectins used. These findings indicate that HSM and its desialylated product (HSM-Tn) are highly useful reagents for the differentiation of Tn and T/Gal specific lectins and for anti-T, Tn and Af monoclonal antibodies.
Mol Immunol 1994 Apr
PMID:Interaction of hamster submaxillary sialyl-Tn and Tn glycoproteins with Gal, GalNAc and GlcNAc specific lectins. 818 85

Wheat germ agglutinin (WGA) elicits a number of biological effects in erythrocytes as a result of specific binding to the transmembrane protein glycophorin A. The structure of co-crystals of WGA (isolectin 1: WGA1) with a bivalent sialoglycopeptide fragment of glycophorin A (T5), determined at 2.0 A resolution, has been further refined and analyzed with respect to ligand-induced changes in the tertiary structure, mobility, solvation, saccharide conformation and protein/saccharide interactions at three independent N-acetyl-D-neuraminic (NeuNAc) binding sites. The final model, which includes the two independent WGA1 monomers (composed of domains A, B, C and D), two positions for bound T5 sialo-tetrasaccharide (NeuNAc-alpha 2,3-Gal-beta 1,3-(alpha 2,6-NeuNAc)GalNAc) and 386 water molecules, refined to a crystallographic R-factor of 17.1% (Fo > 1.0 sigma) and an average temperature factor of 31.99 A2. Comparisons between the tertiary structures of the liganded and unliganded WGA1 dimers indicate that the largest deviations from 2-fold symmetry are localized in domains engaged in sugar binding (B1 and C2) and at the C-terminal domain of monomer II (D2), forming a strong lattice contact. Interactions of the tetrasaccharide with amino acid ligands in the three binding sites and with water were carefully analyzed and compared. Bound conformations of terminal NeuNAc match to within a root-mean-square delta r of 0.3 A. The specificity-determining N-acetyl group superimposes best in comparison with other substituents of the sugar ring. Of the five domain binding sites that are not occupied in this dimeric crosslinked complex, only one is accessible to the NeuNAc monosaccharide as determined from a difference Fourier map at 3.0 A resolution.
J Mol Biol 1993 Jul 20
PMID:Crystallographic refinement and structure analysis of the complex of wheat germ agglutinin with a bivalent sialoglycopeptide from glycophorin A. 834 26

The possibility was explored of synthesizing, from commercially available lipids, high density lipoprotein (HDL)-like particles (neo-HDL) with the same physico-chemical and biological properties as native HDL. A preparation method involving egg yolk phosphatidylcholine, cholesterol, and apoproteins from HDL led to the formation of particles with a composition, size, electrophoretic mobility, and density similar to those of discoidal HDL. In vitro experiments with isolated parenchymal liver cells showed that unlabeled HDL and neo-HDL competed for the same high affinity binding sites as did radiolabeled neo-HDL, whereas an excess of unlabeled low density lipoprotein was ineffective. In vivo experiments with radio-labeled neo-HDL indicated that neo-HDL showed a slow decay upon injection into rats, whereas the liver uptake did not exceed > 10% of the injected dose. The small additional liver uptake of radioactivity from neo-HDL, compared with HDL, was due to enhanced uptake by endothelial and Kupffer cells. Lactosylation of neo-HDL led to a markedly increased decay rate and a rapid uptake by rat liver (80% in 10 min). Parenchymal cells accounted for > 90% of the total liver uptake of radiolabeled lactosylated neo-HDL. Because the liver uptake of lactosylated 125I-neo-HDL could be blocked by preinjection of N-acetylgalactosamine, we conclude that the asialoglycoprotein receptor, which is specifically localized on parenchymal liver cells, is responsible for the avid liver uptake. With a fibroblast cell line transfected with the human asialoglycoprotein receptor, it was found that lactosylated neo-HDL binds with high affinity (Kd, 40 nM), in a galactose-specific way. It can be concluded that, with commercially available lipid components, HDL-like particles (neo-HDL) with virtually the same characteristics as found for native apolipoprotein E-free HDL can be reconstituted. Lactosylated neo-HDL, which is rapidly taken up by galactose-specific receptors on parenchymal liver cells, might be used to transport antiviral drugs specifically to parenchymal liver cells.
Mol Pharmacol 1993 Aug
PMID:Development of lipoprotein-like lipid particles for drug targeting: neo-high density lipoproteins. 835 72

Porphyromonas gingivalis, a bacterium implicated in the pathogenesis of periodontal disease, was found to elaborate an extracellular glycosulfatase enzyme. Upon purification by low temperature acetone fractionation, an active enzyme at 60% acetone was obtained which on SDS-PAGE gave a protein band of 37kDa. The glycosulfatase effectively caused desulfation of galactosyl- and lactosylceramide sulfates (pH 5.0) which contain the sulfate ester groups at C-3 of galactose, a well as proteoglycans (pH 5.7-6.2) of gingival tissue which are rich in N-acetylgalactosamine-4-sulfate, but not the sulfated salivary mucin with the sulfate groups at C-6 of galactose and C-6 of N-acetylglucosamine. The results demonstrate for the first time that P. gingivalis displays glycosulfatase activity and that the disruptive action of this enzyme may be a major factor in the etiology of periodontal disease.
Biochem Mol Biol Int 1993 Apr
PMID:Glycosulfatase activity of Porphyromonas gingivalis a bacterium associated with periodontal disease. 838 37

Cell surface carbohydrates have been shown to be altered during cellular differentiation. Alveolar type II (ATII) cells in culture gradually lose their differentiated phenotype. Therefore, the aim of this study was: (1) to characterize changes in terminal carbohydrates of cell surface glycoproteins of rat ATII cells cultured for 1 to 5 days on plastic, and (2) to assess the concomitant changes in sialidase and sialyltransferase activity of ATII cell homogenates. Cells were surface-labeled with potassium-[3H]-borohydride after oxidation by sodium periodate at millimolar concentrations, galactose oxidase or neuraminidase plus galactose oxidase, allowing for the specific labeling of terminal sialic acids, terminal galactose/N-acetylgalactosamine (Gal/GalNAc), or terminal an penultimate Gal/GalNAc residues, respectively. Glycoproteins were separated by SDS-PAGE. On day 1, cells were heavily coated with sialic acids, since no labeling could be introduced with galactose oxidase alone. From day 1 to day 5, we observed a selective and progressive desialylation of two glycoproteins (200 and 165 kD). At the same time, the ATII cells' sialidase activity (pH 4.2) exhibited an 8-fold increase (60.3 +/- 4.0 pmol/min/mg protein on day 1 versus 406.9 +/- 3.7 pmol/min/mg protein on day 5), whereas the sialyltransferase activity increased 2-fold (212 +/- 8 fmol/min/mg protein on day 1 versus 395 +/- 82 fmol/min/mg protein on day 5) and the supernatant sialidase activity was unchanged (2.8 +/- 0.7 pmol/min/ml on day 5). Thus, the phenotypic changes of ATII cells in primary culture are accompanied by a partial cell surface desialylation and an increase in intracellular sialidase activity.
Am J Respir Cell Mol Biol 1993 Feb
PMID:Cell surface carbohydrates of rat alveolar type II cells in primary culture. 842 6

The basic lectin from winged bean (Psophocarpus tetragonolobus) could be crystallized using polyethyleneglycol (PEG) 4000 (I), PEG 8000 (II) and 2-methylpentane-2,4-diol (MPD) (III) as precipitants. Crystal forms I and II grew in the presence of methyl-alpha-D-galactopyranoside or N-acetylgalactosamine while III grew in the absence of sugar. The three forms have the same space group (P2(1)2(1)2) and similar unit cell dimensions with two dimeric molecules in the asymmetric unit. The unit cell dimensions are a = 156.8 A, b = 89.0 A, c = 73.3 A for I, a = 155.5 A, b = 92.3 A, c = 72.5 A for II and a = 148.3 A, b = 90.7 A, c = 73.8 A for III. The crystals, particularly those grown using PEG 8000, are suitable for high resolution X-ray analysis, which is in progress.
J Mol Biol 1993 Jan 20
PMID:Crystallization and preliminary X-ray studies of the basic lectin from winged bean (Psophocarpus tetragonolobus). 842 64

The equine embryonic capsule replaces the zona pellucida and envelopes the conceptus during the second and third weeks of pregnancy. Although this capsule was described more than 100 years ago, its molecular structure has not been characterized. Here we present evidence that the glycoprotein(s) of the equine capsule resembles those of the mucin glycoprotein family. The resistance of the capsule to chemical and enzymatic solubilization was confirmed, and, as in mucins, protein constituted only 35-40% of its total dry mass. Determination of the sugar composition of the capsule using colorimetric assays and high-performance anion-exchange chromatography also showed it to have mucin-like characteristics. Gal, GalNAc, sulfated sugars, and sialic acid make up a high proportion of the capsular carbohydrate, while GlcNAc, Glc, and Man are minor components. These findings were verified using lectin histochemical staining of frozen sections of conceptuses. The results of amino acid analysis were also consistent with the proposal that the capsular glycoproteins belong to the mucin family. Removal of the covalently bound carbohydrate by beta-elimination under reducing conditions demonstrated that the capsule is O-glycosylated mainly on threonine residues. Affinity chromatography on jacalin-agarose confirmed that, like mucins, the capsular glycoproteins are heavily O-glycosylated. SDS-PAGE analysis revealed a prominent 21-kDa band, specific to the capsule, in preparations solubilized by trypsin but not by other proteases. Characterization of its constituent glycoprotein(s) should be helpful in elucidating the role of the capsule (and analogous blastocyst coverings in other species) during early pregnancy.
Mol Reprod Dev 1993 Mar
PMID:Mucin-like glycoproteins in the equine embryonic capsule. 847 Dec 47

The crystal structure of PR3, a serine proteinase from the azurophilic granules of human polymorphonuclear neutrophils, has been solved by molecular replacement using the human leukocyte elastase structure. The PR3 structure has been refined to an R-factor (= sigma parallel Fo magnitude of-Fc parallel/sigma magnitude of Fo) of 0.201 for all data in the range of 10.0 to 2.2 A resolution. The enzyme was crystallized in space group P21 with four molecules in the asymmetric unit (Vm approximately equal to 2.6 A/Da). The overall fold consists of two domains of beta-barrel structures typical of the chymotrypsin family of serine proteinases. In general, the substrate binding sites, S4 to S3', are more polar than comparable sites in the related proteinase, human leukocyte elastase. The experimentally observed preference of PR3 for small aliphatic residues at the P1 position of a substrate is explained by the Val to Ile substitution at position 190 when compared to the elastase structure. The substitution of Ala by Asp at position 213 at the back of S1 should not affect its specificity greatly, as the Asp side-chain points back into the interior of the protein. The PR3 structure includes a disaccharide unit (N-linked 2-acetamido-2-deoxy-beta-D-glucopyranose and 1,6-linked alpha-L-fucopyranose) covalently attached to Asn 159. The linear antigenic sites of PR3 reported to react with Wegener's granulomatosis autoantibodies occur in regions of the three-dimensional structure that may implicate the inactive pro-form of the enzyme in the pathogenesis of the disease.
J Mol Biol 1996 Aug 16
PMID:The crystal structure of PR3, a neutrophil serine proteinase antigen of Wegener's granulomatosis antibodies. 875 93

Adherence of the enteric protozoan parasite Entamoeba histolytica is mediated by an N-acetyl D-galactosamine (GalNAc)-specific lectin, a heterodimer of heavy (170 kDa) and light (35/31 kDa) subunits. The gene families encoding the lectin subunits were characterized using clamped homogeneous electric field (CHEF) gel electrophoresis in the strain HM1:IMSS. The heavy subunit was shown to be encoded by a family of five hgl genes, which were physically mapped to five distinct HindIII restriction fragments. The light subunit was shown to be encoded by a family of lgl genes located at six loci in the genome. Heavy and light subunit genes did not appear to be linked. Partial sequences of new members of the hgl and lgl gene families were obtained. Several different strains of E. histolytica were found to contain multiple hgl loci in their genomes. Expression of hgl and lgl genes in HM1:IMSS trophozoites was examined under different growth conditions using the reverse transcription-polymerase chain reaction (RT-PCR). mRNA transcripts were detected from three hgl genes and three lgl genes, with no significant differences between cultured amoebae and amoebae from liver abscesses. The complexity of GalNAc lectin gene expression observed suggests distinct biological functions for the products of the individual genes during pathogenesis.
Mol Microbiol 1996 Jan
PMID:Physical mapping and expression of gene families encoding the N-acetyl D-galactosamine adherence lectin of Entamoeba histolytica. 882 39


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