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

To define carbohydrate specificity of Ricinus communis agglutinin (RCA1), the combining site of RCA1 was further characterized by quantitative precipitin (QPA) and precipitin-inhibition assays (QPIA). Among the oligosaccharides tested for QPIA, Gal beta 1-->4GlcNAc (II, human blood group type II precursor sequence) was found to be 7.1 times more active than Gal beta 1-->3GalNAc (T, Thomsen-Friedenreich sequence) and about 1.7 times more active than the other three disaccharides tested--Gal beta 1-->4Man, Gal beta 1-->3DAra and Gal beta 1-->6GalNAc. Gal alpha 1-->4Gal, the receptor of the uropathogenic E. coli ligand was 3.6 times less active than the II sequence. These results indicate that the beta 1-->4 linkage of the terminal Gal to subterminal GlcNAc is important as this beta 1-->4GlcNAc sequence is at least 1.6 times more active than other types of disaccharides. Among the glycoproteins examined for QPA, native and desialized bovine submandibular glycoproteins, native and desialized human plasma alpha 1-acid glycoproteins, as well as crude hog stomach mucin and its three mild acid hydrolyzed products reacted well with the lectin. These glycoproteins precipitated over 75% of the lectin nitrogen added indicating that RCA1 has the ability to recognize Gal beta 1-->4/3GlcNAc and/or the related residues at the non-reducing ends and at positions in the interior of the chains. However, Tn (GalNAc alpha 1-->Ser/Thr sequence) rich glycoproteins such as desialized ovine submandibular glycoprotein and desialized armadillo salivary glycoprotein, in which over 90% of the carbohydrate side chains are Tn determinants with none or only a trace of I/II or T determinants, precipitated poorly with RCA1. From the present and previous results obtained, the carbohydrate specificity of RCA1 can be constructed and summarized in decreasing order by lectin determinants as follows: II (Gal beta 1-->4GlcNAc) > I (Gal beta 1-->3GlcNAc) > E (Gal alpha 1-->4Gal) and B (Gal alpha 1-->3Gal) > T (Gal beta 1-->3GalNAc), while Tn (GalNAc alpha 1-->Ser/Thr) is a poor inhibitor.
Mol Immunol 1993 Mar
PMID:Defining carbohydrate specificity of Ricinus communis agglutinin as Gal beta 1-->4GlcNAc (II) > Gal beta 1-->3GlcNAc (I) > Gal alpha 1-->3Gal (B) > Gal beta 1-->3GalNAc (T). 768 Nov 48

A plasmid that included both an 8.9 kb chromosomal DNA insert containing genes from the rfb cluster of Shigella dysenteriae 1 and a smaller insert containing the rfp gene from a S. dysenteriae 1 multicopy plasmid resulted in efficient expression of O antigen in an rfb-deleted strain of Escherichia coli K-12. Eight genes were identified in the rfb fragment: the rfbB-CAD cluster which encodes dTDP-rhamnose synthesis, rfbX which encodes a hydrophobic protein involved in assembly of the O antigen, rfc which encodes the O antigen polymerase, and two sugar transferase genes. The production of an O antigen also required the E. coli K-12 rfe gene, which is known to encode a transferase which adds N-acetylglucosamine phosphate to the carrier lipid undecaprenol phosphate. Thus Rfe protein appears to function as an analogue of the Salmonella RfbP protein to provide the first sugar of the O unit. Functional analysis of the other genes was facilitated by the fact that partial O units of one, two or three sugars were efficiently transferred to the lipopolysaccharide core. This analysis indicated that the plasmid-encoded Rfp protein is the transferase that adds the second sugar of the O unit while the two rfb transferases add the distal sugars to make an O antigen whose structure is (Rha-Rha-Gal-GlcNAc)n. The use of the rfe gene product as the transferase that adds the first sugar of an O unit is a novel mechanism which may be used for the synthesis of other enteric O antigens.
Mol Microbiol 1993 Jul
PMID:Function of the rfb gene cluster and the rfe gene in the synthesis of O antigen by Shigella dysenteriae 1. 769 19

The activities of Gal beta 1-3(4)GlcNAc alpha 2-3 sialyltransferase and SAT-1 were measured in rat liver Golgi in inflammation; both enzymes decreased by about 50%. This compares with increases of about 3-fold for the Gal beta 1-4GlcNAc alpha 2-6 sialyltransferase. All three sialyltransferases were released from disrupted Golgi membranes by incubation at reduced pH which activates an endogenous cathepsin D which is believed to be the lysosomal enzyme. Pepstatin A was found to block the release of all three sialyltransferases providing support for the role of cathepsin D as the proteinase that clips the catalytic portions of the enzymes from their membrane anchor and stem regions.
Comp Biochem Physiol B Biochem Mol Biol 1995 Feb
PMID:Release of sialyltransferases from rat liver Golgi membranes by a cathepsin D-like proteinase: comparison of the release of Gal beta 1-4GlcNAc alpha 2-6 sialyltransferase, Gal beta 1-3(4)GlcNAc alpha 2-3 sialyltransferase and lactosylceramide alpha 2-3 sialyltransferase (SAT-1). 771 47

Effects of sibiromicyn, distamicyn A and its analogs on binding to DNA and to poly(dA).poly(dT) are reported for a 23-amino acid synthetic zinc-binding peptide, a part of the DNA-binding domain of the transcriptional activator GAL-4. Circular dichroism and fluorometry have shown that the synthetic peptide and two distamicyn A analogs compete for binding sites on DNA and on poly(dA).poly(dT). Antibiotic sibiromycin which forms a covalent bond with a guanine 2-amino group in the minor DNA groove can displace the peptide from a 19 bp self-complementary oligonucleotide serving as a specific target site for Gal-4 protein. The peptide is shown to bind to a glucosylated phage T2 DNA, but its affinity to T2 DNA is weaker than to calf thymus DNA under the same conditions. A method to estimate binding constant and size of the binding site for the synthetic peptide and poly(dA).poly(dT) is proposed based on the binding isotherms of distamycin analogs in the absence and in the presence of the peptide. Using isotherms of binding to poly(dA).poly(dT) for two distamycin analogs with binding constants differing 60-fold, the binding constant of the peptide in the presence of 0.1 M NaCl is estimated as 1.4.10(7)-1.8.10(7) M-1.
Mol Biol (Mosk)
PMID:[A synthetic zinc chelating peptide competes for DNA binding sites with antibiotics, adsorbed in a minor DNA groove]. 778 40

Monoclonal antibodies (MAbs) were generated against Leishmania major promastigote lipophosphoglycan (LPG) to use as tools in defining functional epitopes of this major cell surface glycoconjugate. Epitope mapping of four MAbs, designated 4A2-A2, 2G11-A3, 5E6-D10 and 5E10-F2, revealed that the phosphorylated oligosaccharide repeat unit PO4-6[Gal(beta 1-3)]Gal(beta 1-4)Man alpha 1-, P3, is a highly immunogenic epitope which has previously been demonstrated, by chemical analyses, to be a repeat unit specific to L. major. Two antibodies, 4A2-A2 and 5E10-F2, also recognised the repeat unit PO4-6[Ara(beta 1-2)Gal(beta 1-3)]Gal(beta 1-4)Man alpha 1-, 4Pa, with less affinity than P3, while 2G11-A3 recognised P4a with greater affinity than for P3. The L. major metacyclic-specific antibody 3F12 only recognised repeat units terminating with arabinose residues. In particular, 3F12 recognised P4a, which is upregulated in metacyclic LPG compared to the procyclic form of the molecule. The oligosaccharides P3, P4a and P5a are specific to L. major LPG. The epitopes of 4A2-A2, 2G11-A3, 5E6-D10 and 5E10-F2 were found on the cell surface and in the flagellar pocket of both procyclic and metacyclic V121 promastigotes, but were only detected at very low levels on amastigotes. The repeat unit P3 is able to inhibit attachment of procyclic promastigotes to the midgut of the sandfly vector, but neither Fab fragments of the four antibodies nor purified P3 could inhibit attachment of metacyclic promastigotes to the macrophage cell line J774. It was also shown that human sera from patients with cutaneous leishmaniasis recognised purified P3. The data suggests that while P3 is an immunogen in the natural course of infection of the human host, P3 plays no role in attachment and internalisation of promastigotes into the macrophages of the mammalian host.
Mol Biochem Parasitol 1994 Aug
PMID:Epitope mapping of monoclonal antibodies directed against lipophosphoglycan of Leishmania major promastigotes. 780 69

Recent studies have extended our knowledge regarding the contents of mammalian cortical granules (CG) and their function in postfertilization events. Cytochemical staining has demonstrated the presence of carbohydrates within mammalian CG, and lectin-binding studies have shown that these carbohydrates include alpha-D-mannose, alpha-D-GalNAc, and galactose residues in the hamster, alpha-D-mannose in the mouse and cat, and beta-D-Gal(1,3)-D-GalNAc in the pig. Following fertilization and artificial activation, mannosylated material is released from CG and can be found on the oolemma and within the perivitelline space (PVS) of hamster oocytes. Fertilized or artificially activated rabbit, mouse, and human oocytes also release mannosylated, fucosylated and sialylated, and fucosylated material, respectively, which localizes to the oolemma. These glycosylated materials are probably of CG origin, although they have not been directly localized to the CG in rabbit, mice, and humans. The function(s) of the glycosylated material released from mammalian oocytes is not known, although it may participate in blocking polyspermy at the level of the plasma membrane, PVS, and/or zona pellucida (ZP), or it may facilitate preimplantation embryonic development. Proteinases, including tissue plasminogen activator, are also released from mammalian oocytes following fertilization and artificial activation, suggesting that they are of CG origin. These proteinases modify the ZP such that it is no longer receptive to sperm, and some proteinases have been suggested to bring about ZP hardening (an increased resistance to denaturing agents) by an unknown mechanism. Mouse ZP may also be hardened by an ovoperoxidase (cross-links tyrosine residues) cytochemically identified in mouse CG and CG exudate. The phenomena of ZP hardening in mammalian zygotes is not well understood but is likely to function in blocking polyspermic penetration of the ZP and/or in protecting embryos during preimplantation development. Recently, a 75 kD protein (p75) has been immunocytochemically localized to mouse CG and to the PVS of fertilized oocytes and two-cell embryos. The identity and function of p75 remains to be determined. Heparin binding placental protein may also be a CG component, since it is released from hamster oocytes following fertilization. It has not, however, been directly demonstrated to be a CG component, and its functions in fertilization and/or early embryonic development have yet to be defined.
Mol Reprod Dev 1994 Dec
PMID:Mammalian cortical granules: contents, fate, and function. 789 93

Pseudomonas aeruginosa employs pili to mediate adherence to epithelial cell surfaces. The pilus adhesin of P. aeruginosa strains PAK and PAO has been shown to bind to the glycolipid asialo-GM1 (Lee et al., 1994--accompanying article). PAK and PAO pili were examined for their abilities to bind to the synthetic beta GalNAc(1-4)beta Gal (a minimal structural carbohydrate receptor sequence of asialo-GM1 and asialo-GM2 proposed by Krivan et al., 1988a) using solid-phase binding assays. Both pili specifically bound to beta GalNAc(1-4)beta Gal. The binding of beta GalNAc(1-4)beta Gal-Biotin to the immobilized PAK and PAO pili was inhibited by corresponding free pili. The receptor binding domain of the PAK pilus resides in the C-terminal disulphide-looped region (residues 128-144) of the pilin structural subunit (Irvin et al., 1989). Biotinylated synthetic peptides corresponding the C-terminal residues 128-144 of P. aeruginosa PAK and PAO pilin molecules were shown to bind to the beta GalNAc(1-4)beta Gal-(bovine serum albumin (BSA)). The binding of biotinylated peptides to beta GalNAc(1-4)beta GAL-BSA was inhibited by PAK pili, Ac-KCTSDQDEQFIPKGCSK-OH (AcPAK(128-144)ox-OH) and Ac-ACKSTQDPMFTPKGCDN-OH (AcPAO(128-144)ox-OH) peptides. (In these peptides Ac denotes N alpha-acetylation of the N-terminus, -OH means a peptide with a free alpha-carboxyl group at the C-terminus and the 'ox' denotes the oxidation of the sulphhydryl groups of Cys-129 and Cys-142.) Both acetylated peptides were also able to inhibit the binding of beta GalNAc(1-4)beta Gal-biotin to the corresponding BSA-Peptide(128-144)ox-OH conjugates.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Microbiol 1994 Feb
PMID:The pili of Pseudomonas aeruginosa strains PAK and PAO bind specifically to the carbohydrate sequence beta GalNAc(1-4)beta Gal found in glycosphingolipids asialo-GM1 and asialo-GM2. 791 Sep 39

Galactose transport and metabolism in Escherichia coli involves a multicomponent amphibolic pathway. Galactose transport is accomplished by two different galactose-specific transport systems. At least four of the genes and operons involved in galactose transport and metabolism have promoters containing similar regulatory sequences. These sequences are recognized by at least three regulators, Gal repressor (GalR), Gal isorepressor (GalS) and cAMP receptor protein (CRP), which modulate transcription from these promoters. The negative regulators, GalR and GalS, discriminate between utilization of the high-affinity (regulated by GalS) and low-affinity (regulated by GalR) transport systems, and modulate the expression of genes for galactose metabolism in an overlapping fashion. GalS is itself autogenously regulated and CRP dependent, while the gene for GalR is constitutive. The gal operon encoding the enzymes for galactose metabolism has two promoters regulated by CRP in opposite ways; one (P1) is stimulated and the other (P2) inhibited by CRP. Both promoters are strongly repressed by GalR but weakly by GalS. All but one of the constituent promoters of the gal regulon have two operators. The gal regulon has the potential to coordinate galactose metabolism and transport in a highly efficient manner, under a wide variety of conditions of galactose availability.
Mol Microbiol 1993 Oct
PMID:The galactose regulon of Escherichia coli. 793 15

Escherichia coli strains causing acute pyelonephritis often express multiple fimbrial types and haemolysin, which may contribute to their ability to adhere to, and interact with, kidney epithelial cells. Strain CFT073, a pap+, sfa+, pil+, hly+ pyelonephritis strain, previously established as virulent in the CBA mouse model of ascending urinary tract infection and cytotoxic for cultured human renal epithelial cells, was selected for construction of isogenic strains. From a gene bank of this strain, two distinct copies of the pap operon were isolated. The two P-fimbrial determinants were subcloned into pCVD442, a positive selection suicide vector containing the sacB gene of Bacillus subtilis. Deletion mutations were introduced into each of the two constructs, within papEFG of one operon and papDEFG of the other. Suicide vectors carrying pap deletions were mobilized from E. coli SM10 lambda pir into CFT073 (NalR) and cointegrates were passaged on non-selective medium. The first pap mutation was identified by screening a Southern blot of DNA from sucrose-resistant colonies using a papEFG probe. This mutant retained the MRHA+ phenotype since a second functional copy of pap was still present. A double pap-deletion mutant, UPEC76, confirmed by Southern blotting, was unable to agglutinate human type O erythrocytes or alpha Gal(1-4)beta Gal-coated latex beads. CBA mice (N = 100) were challenged transurethrally with 10(5), 10(6), 10(7), or 10(9) cfu of strains CFT073 or UPEC76. After one week, quantitative cultures of urine, bladder, and kidney were done and histologic changes were examined. No substantive differences in organism concentration or histological findings between parent and mutant were detected in urine, bladder, or kidney at any challenge concentration. We conclude that adherence by P fimbriae of uropathogenic E. coli strain CFT073 plays only a subtle role in the development of acute pyelonephritis in the CBA mouse model.
Mol Microbiol 1993 Oct
PMID:Isogenic P-fimbrial deletion mutants of pyelonephritogenic Escherichia coli: the role of alpha Gal(1-4) beta Gal binding in virulence of a wild-type strain. 796 11

Receptor-bound growth factors elicit intracellular signals that lead to the phosphorylation and activation of numerous intracellular kinases and transcription factors with consequent changes in patterns of gene expression. Several oncogene products are able to mimic these signals, resulting in cell transformation and proliferation. For example, the introduction of oncogenic forms of Raf-1 kinase into fibroblasts induces transformation and leads to the constitutive expression of, among others, the c-fos proto-oncogene. Here it is shown that the elevation of c-fos promoter activity brought about by v-raf is mediated by TCF/Elk-1, which forms a ternary complex with SRF at the serum response element and is a substrate for mitogen-activating protein kinases in vitro. In NIH 3T3 fibroblasts, v-raf activates Erk2, and overexpression of an interfering mutant of Erk2 both blocks the ability of v-raf to activate the c-fos promoter and suppresses transformation. Mutation of individual mitogen-activating protein kinase phosphoacceptor sites in TCF/Elk-1 also compromises v-raf-activated expression of a Gal-Elk/Gal-chloramphenicol acetyltransferase reporter system. However, in at least one instance the introduction of glutamate, but not aspartate, at a phosphoacceptor site is compatible with activation. These results provide compelling evidence that phosphorylation of TCF/Elk-1 by Erk2 is a major link in the Raf-1 kinase-dependent signal transduction pathway that activates c-fos expression.
Mol Cell Biol 1994 Jul
PMID:Inhibition of v-raf-dependent c-fos expression and transformation by a kinase-defective mutant of the mitogen-activated protein kinase Erk2. 800 80


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>