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At least 73 records · Page 4Linked to original sources
PubMed1997

Demonstration of peripheral fucose units in N-linked glycans of human immunodeficiency virus type 1 gp 120: effects on glycoprotein conformation.

Fucosylated N-linked glycans are important constituents of membrane glycoproteins, owing to their significance as biologically active ligands for several selectins and their role in modulating protein conformation of viral glycoproteins. The human immunodeficiency virus type 1 (HIV-1) glycoprotein contains more than 30 different glycan structures but so far fucose was found associated solely with the innermost GlcNAc of N-linked glycans. In the present report we determined whether fucose units also were linked to the distal GlcNAc via alpha(1-3) or alpha(1-4) linkages in N-linked glycans of gp 120. [3H]-fucose labelled gp 120 was subjected to endoglycosidase F digestion, releasing diantennary complex type N-linked glycans, but leaving the inner polypeptide-bound carbohydrates, GlcNAc and possibly associated fucose units, intact. Gel filtration of the digested material revealed that [3H]-fucose label was released from gp 120 by this treatment, indicating presence of peripheral fucose units. Furthermore, [3H]-focuse label was also released by treatment of the labelled gp 120 with an alpha-L-fucosidase specifically removing fucose in alpha(1-3) and alpha(1-4) linkages. Altogether the results indicated presence of fucose units linked to peripheral GlcNAc of gp 120 N-linked glycans. We have earlier shown that other peripheral carbohydrate determinants, i.e. beta(1-4)-galactose on N-linked glycans, maintain a correct antigenic conformation of gp 120. Using a coupled ELISA system, where changes in antigenic behaviour of a viral glycoprotein were correlated to stepwise elimination of peripheral monosaccharides from N-linked glycans, we found that treatment of gp 120 with a pan-specific alpha-fucosidase as well as an enzyme specific for alpha(1-3)- or alpha(1-4)-linked fucose disclosed a hidden linear epitope situated in the gp 120 C2 region. The effects of the general fucosidase on epitope exposure was more prominent than those obtained with the enzyme with narrow specificity, suggesting that peripheral and inner fucose units co-operate in the maintenance of gp 120 conformation.

Animals↗
PubMed1982

Membrane-associated, fucose-containing glycoproteins and glycolipids of cultured epithelial cells from human colonic adenocarcinoma and fetal intestine.

Fucose-containing glycoproteins and glycolipids were compared in three human colon cancer cell lines and five human fetal intestinal epithelial cell lines. Cells were labeled by culturing cells in the presence of L-[3H]-fucose. Fucose was incorporated into both the membrane and cytoplasmic fractions of all three colon cancer cell lines to a much lesser extent than into fetal cells. When the relative fucose labeling of glycolipids and glycoproteins were examined, a much greater proportion of fucose labeling in the membrane was associated with lipid in colon cancer cells (11.6-16.7%) compared to fetal intestinal cells (1.3-2.5%). Fluorographic analysis of SDS-polyacrylamide gel electrophoresis of fucose-labeled glycoproteins revealed a rather uniform labeling pattern of fetal intestinal cells which was distinct from those of colon cancer cells. Thin-layer chromatographic analysis of fucose labeled glycolipids of all three colon cancer cell lines indicated the presence of fucose-containing glycolipids with carbohydrate chain lengths greater than five sugars. Glycolipids of the SKCO-1 cells in particular appear to consist predominantly of complex fucose-containing glycolipids. These results indicate that significant qualitative differences in the fucose-containing glycoproteins and glycolipids exist between the membranes of human colon cancer cells and fetal intestinal cells and that complex fuco-glycolipids with long carbohydrate side chains are present in the three human colon cancer cell lines.

Adenocarcinoma↗
PubMed1994

Decreased myo-inositol uptake is associated with reduced bradykinin-stimulated phosphatidylinositol synthesis and diacylglycerol content in cultured neuroblastoma cells exposed to L-fucose.

L-Fucose is a potent, competitive inhibitor of myo-inositol transport by cultured mammalian cells. Chronic exposure of neuroblastoma cells to L-fucose causes a concentration-dependent decrease in myo-inositol content, accumulation, and incorporation into phosphoinositides. In these studies, L-fucose supplementation of culture medium was used to assess the effect of decreased myo-inositol metabolism and content on bradykinin-stimulated phosphatidylinositol synthesis and diacylglycerol production. Chronic exposure of cells to 30 mM L-fucose caused a sustained decrease in bradykinin-stimulated, but not basal, 3H-inositol phosphate release and 32P incorporation into phosphatidylinositol in cells incubated in serum-free, unsupplemented medium. In addition, 32P incorporation into phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate was not altered in L-fucose-conditioned cells. Acute exposure of cells to serum-free medium containing 30 mM L-fucose did not affect either basal or bradykinin-stimulated 32P incorporation into phosphatidylinositol. Basal diacylglycerol content was decreased by 20% in cells chronically exposed to 30 mM L-fucose, although analysis of the molecular species profile revealed no compositional change. Bradykinin stimulated diacylglycerol production in neuroblastoma cells by increasing the hydrolysis of both phosphoinositides and phosphatidylcholine. Bradykinin-stimulated production of total diacylglycerol was similar for control and L-fucose-conditioned cells. However, there was a decrease in the bradykinin-induced generation of the 1-stearoyl-2-arachidonoyl diacylglycerol molecular species in the cells chronically exposed to 30 mM L-fucose. This molecular species accounts for about 70% of the composition of phosphoinositides, but only 10% of phosphatidylcholine. The results suggest that a decrease in myo-inositol uptake results in diminished agonist-induced phosphatidylinositol synthesis and phosphoinositide hydrolysis in cultured neuroblastoma cells grown in L-fucose-containing medium.

Animals↗
PubMed2002

Fringe modifies O-fucose on mouse Notch1 at epidermal growth factor-like repeats within the ligand-binding site and the Abruptex region.

Fringe plays a key role in the specification of boundaries during development by modulating the ability of Notch ligands to activate Notch receptors. Fringe is a fucose-specific beta1,3-N-acetylglucosaminyltransferase that modifies O-fucose moieties on the epidermal growth factor-like (EGF) repeats of Notch. To investigate how the change in sugar structure caused by Fringe modulates Notch activity, we have analyzed the sites of O-fucose and Fringe modification on mouse Notch1. The extracellular domain of Notch1 has 36 tandem EGF repeats, many of which are predicted to be modified with O-fucose. We recently proposed a broadened consensus sequence for O-fucose, C(2)X(3-5)(S/T)C(3) (where C(2) and C(3) represent the second and third conserved cysteines), significantly expanding the potential number of modification sites on Notch. Here we demonstrate that sites predicted using this broader consensus sequence are modified with O-fucose on mouse Notch1, and we present evidence suggesting that the consensus can be further refined to C(2)X(4-5)(S/T)C(3). In particular, we demonstrate that EGF 12, a portion of the ligand-binding site, is modified with O-fucose and that this site is evolutionarily conserved. We also show that endogenous Fringe proteins in Chinese hamster ovary cells (Lunatic fringe and Radical fringe) as well as exogenous Manic fringe modify O-fucose on many but not all EGF repeats of mouse Notch1. These findings suggest that the Fringes show a preference for O-fucose on some EGF repeats relative to others. This specificity appears to be encoded within the amino acid sequence of the individual EGF repeats. Interestingly, our results reveal that Manic fringe modifies O-fucose both at the ligand-binding site (EGF 12) and in the Abruptex region. These findings provide insight into potential mechanisms by which Fringe action on Notch receptors may influence both the affinity of Notch-ligand binding and cell-autonomous inhibition of Notch signaling by ligand.

Amino Acid Sequence↗
PubMedDate not supplied

Enhancement of glutamate release by L-fucose changes effects of glutamate receptor antagonists on long-term potentiation in the rat hippocampus.

In previous studies L-fucose has been shown to facilitate long-term memory formation and to enhance and prolong long-term potentiation (LTP). To search for possible presynaptic or postsynaptic mechanisms that are affected by L-fucose, we examined the effect of L-fucose on (1) inhibition of LTP induction via glutamate receptors by antagonists, (2) paired-pulse facilitation, and (3) presynaptic transmitter release. Coapplication of 0.2 mM L-fucose with the competitive N-methyl-D-aspartate (NMDA) receptor antagonist, D-2-amino-5-phosphonovalerate (AP5), or coapplication of 0.2 mM L-fucose in the presence of an inhibitor for class I/II metabotropic glutamate receptors, (S)-alpha-methyl-4-carboxyphenylglycine (MCPG), reversed LTP blockade in the CA1-region of hippocampal slices. In contrast, L-fucose had no effect on the LTP blockade by the noncompetitive NMDA ion-channel blocker (5R,10S)-(+)-5-Methyl-10, 11-dihydro-5H-dibenzo[a,d]cyclohepten-5, 10-imine hydrogen maleate (MK-801). Paired-pulse facilitation, which is a primarily presynaptic phenomenon of short-term plasticity, was decreased in the presence of 0.2 mM L-fucose. Furthermore, L-fucose enhanced the K(+)-stimulated release of [(3)H]-D-aspartate from preloaded hippocampal slices in a concentration-dependent manner. These observations demonstrate an influence of L-fucose on transmitter release that in turn can increase transmitter availability at postsynaptic glutamate receptors. This effect of L-fucose may contribute to the LTP facilitation seen in vitro and in vivo as well as to improvement in memory formation.

2-Amino-5-phosphonovalerate↗
PubMed2005

Enhanced natural killer cell binding and activation by low-fucose IgG1 antibody results in potent antibody-dependent cellular cytotoxicity induction at lower antigen density.

PURPOSE: Recent studies have revealed that fucose removal from the oligosaccharides of human IgG1 antibodies results in a significant enhancement of antibody-dependent cellular cytotoxicity (ADCC) via improved IgG1 binding to FcgammaRIIIa. In this report, we investigated the relationship between enhanced ADCC and antigen density on target cells using IgG1 antibodies with reduced fucose. EXPERIMENTAL DESIGN: Using EL4 cell-derived transfectants with differential expression levels of exogenous human CC chemokine receptor 4 or human CD20 as target cells, ADCC of fucose variants of chimeric IgG1 antibodies specific for these antigens were measured. We further investigated IgG1 binding to natural killer (NK) cells and NK cell activation during ADCC induction to elucidate the mechanism by which low-fucose IgG1 induces ADCC upon target cells with low antigen expression. RESULTS: Low-fucose IgG1s showed potent ADCC at low antigen densities at which their corresponding high-fucose counterparts could not induce measurable ADCC. The quantitative analysis revealed that fucose depletion could reduce the antigen amount on target cells required for constant degrees of ADCC induction by 10-fold for CC chemokine receptor 4 and 3-fold for CD20. IgG1 binding to NK cells was increased by ligating IgG1 with clustered antigen, especially for low-fucose IgG1. Up-regulation of an activation marker, CD69, on NK cells, particularly the CD56(dim) subset, in the presence of both the antibody and target cells was much greater for the low-fucose antibodies. CONCLUSIONS: Our data showed that fucose removal from IgG1 could reduce the antigen amount required for ADCC induction via efficient recruitment and activation of NK cells.

Antibody-Dependent Cell Cytotoxicity↗
PubMedDate not supplied

Studies on corneal wound healing. Effect of fucose on iodine vapor-burnt rabbit corneas.

Corneal wound healing often leads to the development of scar tissue with loss of transparency. Reconstitution of transparent corneal stroma depends on the regulation of the biosynthetic activities of postlesional keratocytes and also to a large extent on the limitation of matrix degradation, attributed essentially to the upregulation of matrix metalloproteases and especially MMP-9. Using a standardized method for the production of reproducible corneal lesions by burning with iodine vapors, we could show that the local application of 0.5 mg/ml L-fucose reduced significantly MMP-9 upregulation and accelerated the recovery of the epithelial layer of the cornea. The iodine vapor used in the experiments produces a rapid loss of epithelium with no or slight effect below the basement membrane. A relatively rapid regrowth of epithelium was observed. The speed of this reepithelialization was stimulated by the local application of fucose. At 48 h after burn, there was a difference between fucose-treated and control corneas (epithelial thickness was about 50 mum for fucose-treated corneas and 37 microm for control corneas). Culture media of in vivo fucose-treated corneas showed an important decrease of MMP-9 activity (-51%, n = 6, p < 0.01). It appears that the in vivo fucose treatment reduced the MMP-9 activity released in the media. This effect is significant 24 h after iodine vapor burn. In order to study the effect of fucose on normal corneas, it was added to rabbit as well as human cornea explant cultures, and the production and release of MMP-9 was determined by zymography. Fucose at a concentration of 0.5 mg/ml produced a 70% decrease of MMP-9 activity released in the medium by corneal explant cultures. Other mono- and oligosaccharides were also tested. Besides lactose, fucose-rich oligosaccharides also produced significant inhibition. Galactose, melibiose, mannose and glucose were inactive. These results justify the use of fucose for the local treatment of corneal wounds.

Animals↗
PubMed1991

Serum fucose levels in gynaecological disorders including carcinoma cervix.

Serum protein bound fucose levels and the ratio between serum protein bound fucose and total serum protein were determined in 40 healthy females, 60 patients with benign gynaecological disorders and 50 patients with previously untreated cases of carcinoma cervix. The mean serum fucose level in healthy subjects was 8.96 mg% and the ratio between serum protein bound fucose and total serum protein was 1.29 x 10(-3). Mean serum fucose level in patients with benign gynaecological disorders was 9.42 mg% and the ratio between serum protein bound fucose and total serum protein was 1.42 x 10(-3). In stage I and II carcinoma cervix patients mean serum fucose was 11.92 mg% and the ratio between serum protein bound fucose and total serum protein was 1.68 x 10(-3). In stage III and IV carcinoma cervix patients the mean serum fucose was 17.76 mg% and the ratio between serum protein bound fucose and total serum protein was 2.64 x 10(-3).

Blood Proteins↗
PubMed1998

GDP-fucose synthetase from Escherichia coli: structure of a unique member of the short-chain dehydrogenase/reductase family that catalyzes two distinct reactions at the same active site.

BACKGROUND: . In all species examined, GDP-fucose is synthesized from GDP-mannose in a three-step reaction catalyzed by two enzymes, GDP-mannose 4,6 dehydratase and a dual function 3, 5-epimerase-4-reductase named GDP-fucose synthetase. In this latter aspect fucose biosynthesis differs from that of other deoxy and dideoxy sugars, in which the epimerase and reductase activities are present as separate enzymes. Defects in GDP-fucose biosynthesis have been shown to affect nodulation in bacteria, stem development in plants, and are associated with the immune defect leukocyte adhesion deficiency type II in humans. RESULTS: . We have determined the structure of GDP-fucose synthetase from Escherichia coli at 2.2 A resolution. The structure of GDP-fucose synthetase is closely related to that of UDP-galactose 4-epimerase and more distantly to other members of the short-chain dehydrogenase/reductase family. We have also determined the structures of the binary complexes of GDP-fucose synthetase with its substrate NADPH and its product NADP+. The nicotinamide cofactors bind in the syn and anti conformations, respectively. CONCLUSIONS: . GDP-fucose synthetase binds its substrate, NADPH, in the proper orientation (syn) for transferring the 4-pro-S hydride of the nicotinamide. We have observed a single binding site in GDP-fucose synthetase for the second substrate, GDP-4-keto,6-deoxy-mannose. This implies that both the epimerization and reduction reactions occur at the same site in the enzyme. As is the case for all members of the short-chain family of dehydrogenase/reductases, GDP-fucose synthetase retains the Ser-Tyr-Lys catalytic triad. We propose that this catalytic triad functions in a mechanistically equivalent manner in both the epimerization and reduction reactions. Additionally, the X-ray structure has allowed us to identify other residues that are potentially required for substrate binding and catalysis.

Amino Acid Sequence↗
PubMed1980

Enzymic determination of urinary free L-fucose.

Conditions necessary for the precise measurement of free L-fucose in urine by an enzymic method using L-fucose dehydrogenase have been studied. The normal urinary levels of L-fucose were 16.4 /+- 9.1 micrograms/ml in children (22.2 /+- 6.5 micrograms/mg of creatinine) and 17.7 /+- 8.5 micrograms/ml in adults (16.6 /+- 5.7 micrograms/mg of creatinine). There was a close correlation between the concentration of free L-fucose and that of creatinine. A close correlation was also found between the concentration of free L-fucose and alpha-L-fucosidase activity. Thus, it was suggested that the free L-fucose in urine reflected the metabolism of L-fucose or L-fucose-containing glycoconjugates. In a preliminary screening test, several urine samples which showed high concentrations of free L-fucose, namely cases of "fucosuria" were found.

Adult↗
PubMed1996

Reduced Na+/K+ adenosine triphosphatase activity and motor nerve conduction velocity in L-fucose-fed rats is reversible after dietary normalization.

Development of early defects in diabetic neuropathy has been linked to metabolic abnormalities and is considered reversible. To further address some of the questions concerning the contribution by metabolic derangements to the development of neural defects and reversibility, we have developed an animal model, by feeding rats a diet containing 20% L-fucose, that develops neural defects similar to those that occur in streptozotocin-induced diabetic rats. After 6 weeks on a 20% L-fucose diet, myo-inositol content and Na+/K+ adenosine triphosphatase (ATPase) activity of the sciatic nerve were significantly reduced, as was the motor nerve conduction velocity (MNCV). L-Fucose is a monosaccharide that occurs in low concentrations in normal serum but is increased in diabetic patients. In cultured cells, L-fucose, at concentrations that occur in diabetic circulation, is a competitive inhibitor of myo-inositol uptake. The purpose of the present study was to compare the sequential pattern of the reversibility of the slowing of MNCV with ouabain-inhibited sciatic nerve Na+/K+ ATPase activity and myo-inositol content in rats fed a diet containing 20% L-fucose for a period of 6 weeks followed by a normal diet lasting up to 2 weeks. Unbound L-fucose levels in the serum returned to normal in less than 24 hours of the rats being placed on the normal diet. Normalization of slowed MNCV after removing L-fucose-fed rats from the L-fucose diet followed a pattern of recovery similar to the recovery of sciatic nerve ouabain-inhibited Na+/K+ ATPase activity, with complete recovery occurring within 7 days of the rats being placed on the normal diet. In contrast, myo-inositol content of the sciatic nerve remained decreased following 3 days on the normal diet, and required 14 days for complete normalization. Results from these studies suggest that a causal relationship may exist for reduced Na+/K+ ATPase activity and MNCV in L-fucose-fed rats, and that a measurable decrease in myo-inositol content may not be necessary for the development of these defects in the sciatic nerve.

Animals↗
PubMed1997

Fucose levels in sera and in tumours of colorectal adenocarcinoma patients.

Fucose levels were determined in normal and tumour-derived tissues from patients with colorectal adenocarcinoma. Total, free and bound fucose were significantly higher (P < 0.001) in the tumoral tissue. Comparison of serum fucose levels between patients with colorectal cancer and control subjects indicated no statistically significant differences in total, free and bound fucose expressed as nmol/ml serum. However, when total and bound fucose were normalized to total protein (nmol/mg protein), an elevation in both parameters was found in colorectal cancer patients, although only that for total fucose was statistically significant (P < 0.001). A clear association between fucose content and clinical stage of patients according to the Dukes' classification can not be established, although patients at stage C showed higher levels of fucose both in serum and tissue. The current investigation provides direct evidence of a relationship between the elevation of fucose and the presence of tumour in colorectal cancer patients.

Adenocarcinoma↗
PubMed2005

Highly conserved O-fucose sites have distinct effects on Notch1 function.

The extracellular domain of mouse Notch1 contains 36 tandem epidermal growth factor-like (EGF) repeats, many of which are modified with O-fucose. Previous work from several laboratories has indicated that O-fucosylation plays an important role in ligand mediated Notch activation. Nonetheless, it is not clear whether all, or a subset, of the EGF repeats need to be O-fucosylated. Three O-fucose sites are invariantly conserved in all Notch homologues with 36 EGF repeats (within EGF repeats 12, 26, and 27). To investigate which O-fucose sites on Notch1 are important for ligand-mediated signaling, we mutated the three invariant O-fucose sites in mouse Notch1, along with several less highly conserved sites, and evaluated their ability to transduce Jagged1- and Delta1-mediated signaling in a cell-based assay. Our analysis revealed that mutation of any of the three invariant O-fucose sites resulted in significant changes in both Delta1 and Jagged1 mediated signaling, but mutations in less highly conserved sites had no detectable effect. Interestingly, mutation of each invariant site gave a distinct effect on Notch function. Mutation of the O-fucose site in EGF repeat 12 resulted in loss of Delta1 and Jagged1 signaling, while mutation of the O-fucose site in EGF repeat 26 resulted in hyperactivation of both Delta1 and Jagged1 signaling. Mutation of the O-fucose site in EGF repeat 27 resulted in faulty trafficking of the Notch receptor to the cell surface and a decreased S1 processing of the receptor. These results indicate that the most highly conserved O-fucose sites in Notch1 are important for both processing and ligand-mediated signaling in the context of a cell-based signaling assay.

Animals↗
PubMed1980

Carcinoembryonic antigen and L-fucose in malignant and benign mammary disease.

A prospective study of 123 patients was undertaken to determine whether carcinoembryonic antigen (CEA) or L-fucose could be used as "tumor markers" to distinguish patients who had mammary cancer (41) from patients who had benign mammary disease (41) and patients who did not have mammary cancer (41). The predictive value of positive test results for both L-fucose and CEA was lower for patients who smoked than for those who did not. The sensitivities of CEA and L-fucose indicators are both below 55%. There were frequent false-positive and false-negative results. A substantial overlap in the levels of CEA and L-fucose was found for the patients who had mammary cancer and those who had benign mammary disease. CEA and L-fucose performed similarly in distinguishing cancer from benign disease. For patients who smoked, however, the predictive value of L-fucose was only 44%. The effect of smoking on L-fucose levels may account for discrepancies in L-fucose data reported in previous studies of mammary cancer. Neither CEA nor L-fucose were found to be of value in screening for mammary cancer.

Breast Diseases↗
PubMed1998

Fucose-specific adhesins on germ tubes of Candida albicans.

Lectin-like adhesins of hyphal-form Candida albicans were investigated by conventional fluorescence microscopy, fluorescence microscopy with image analysis, spectrofluorimetry and flow cytometry. Labelling was done with neoglycoprotein probes consisting of sugars (fucose, mannose, glucose, galactose, lactose) covalently linked to bovine serum albumin (BSA), which itself was labelled with fluorescein. The fucose probe bound to both the yeast and germ-tube portions of hyphal-form cells, not especially at the tip, but in the adjacent region of the germ-tube portion. Probes with the other sugars did not label the hyphal-form cells. Fucose-probe binding to the cells was optimal at pH 5.0 in citrate buffer, and was a time-dependent reaction requiring 30-60 min and reaching saturation concentration at 100 microg ml(-1). Each hyphal-form cell of C. albicans grown in 199 medium was calculated to have about 2 x 10(7) fucose probe-binding sites. There appeared to be no requirement for Ca2+ or Mg2+ in binding. Binding of the fucose probe to the hyphal-form cells was higher at 37 degrees C than at 22 degrees C or 4 degrees C. Fluorescence intensity of the fucose-labelled yeast forms was not increased over the hyphal-form cells. A germ-tube-deficient mutant when exposed to hyphal-form growth conditions for 2 h showed much less binding of the fucose probe than the wild-type which produced germ tubes. Confirmation of specificity and the need for a carrier molecule was obtained by showing that Fuc-BSA (without fluorescein) effectively inhibited the binding of the fucose probe, although L-fucose itself was inactive, as was Gal-BSA.

Candida albicans↗
PubMed1977

Regulatory changes in the fucose system associated with the evolution of a catabolic pathway for propanediol in Escherichia coli.

Wild-type strains of Escherichia coli are unable to use L-1,2-propanediol as a carbon and energy source. Strain 3, a mutant selected for the ability to grow on this compound at progressively more rapid rates, synthesizes constitutively a nicotinamide adenine dinucleotide-linked propanediol oxidoreductase. This enzyme is normally synthesized during anaerobic growth on L-fucose when it functions as a lactaldehyde reductase. Propanediol, the end product of this fermentation process, escapes irretrievably into the medium. The propanediol-utilizing mutant can no longer grow on fucose in either the presence or absence of molecular oxygen. In the present study nine independent lines of propanediol-positive mutants were characterized. One mutant, strain 418, attained a propanediol growth rate close to that of strain 3 without loss of the ability to grow on fucose. In all cases examined, however, prolonged selection on propanediol did result in the emergence of fucose-negative mutants. All of these mutants had enzyme patterns similar to that of strain 3; namely, fucose permease, fucose isomerase, and fuculose kinase were noninducible, whereas fuculose 1-phosphate aldolase was constitutive. In strain 418 and in the fucose-positive predecessors of the other mutants, the first four enzymes in the pathway remained inducible, as in the wild-type strain. Improvements in the growth rate on propanediol appeared to reflect principally the increased activity level of the oxidoreductase during the early stages of evolution. According to transductional analysis, the mutations affecting the ability to grow on propanediol and those that affect the expression of the first enzymes in the fucose pathway were very closely linked. The loss of the ability to grow on fucose is thought to be a mechanistic consequence incidental to the remodeling of the regulatory system in favor of the utilization of the novel carbon source.

Alcohol Oxidoreductases↗
PubMed1993

Reduced motor nerve conduction velocity and Na(+)-K(+)-ATPase activity in rats maintained on L-fucose diet. Reversal by myo-inositol supplementation.

L-Fucose is a monosaccharide that occurs in low concentrations in normal serum but has been shown to be increased in diabetic individuals. In cultured mammalian cells, L-fucose is a potent competitive inhibitor of myo-inositol transport. Abnormal myo-inositol metabolism has been proposed to be a factor in the development of diabetic complications. To test the hypothesis that myo-inositol deficiency may be responsible for the electrophysiological and biological defects in diabetic neuropathy, rats were fed a diet containing 10 or 20% L-fucose for a period of 6 wk. After 3 wk, the L-fucose diets in two groups of rats were supplemented with 1% myo-inositol. At the end of the study protocol, motor nerve conduction velocity, sciatic nerve tissue Na(+)-K(+)-ATPase activity, and myo-inositol content were determined. These results were compared with those of STZ-induced diabetic rats fed either a normal diet or a diet containing 1% myo-inositol or with those given 450 mg/kg body wt of sorbinil. Serum L-fucose levels were significantly increased in rats fed a diet containing 10 or 20% L-fucose. In comparison, the serum L-fucose levels in the diabetic rats were increased to a lesser extent. Motor nerve conduction velocity was significantly slower in rats fed a 10 or 20% L-fucose diet. Sciatic nerve composite and ouabain-sensitive Na(+)-K(+)-ATPase activity and myo-inositol content was also significantly decreased. Supplementation of 1% myo-inositol to the L-fucose-containing diet restored nerve myo-inositol levels and significantly improved Na(+)-K(+)-ATPase activity and motor nerve conduction velocity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2004

Prediction of 3-D structures of fucose-binding proteins and structural analysis of their interaction with ligands.

The importance of fucose-binding proteins stems from the presence of fucose as terminal sugars in H and Lewis (a) blood groups. Recently, the structure of a complex between Anguilla anguilla agglutinin (AAA) and alpha-L-fucose has been worked out at 1.9 A resolution. The structure of AAA characterizes the novel fold of an entire lectin family. In the present study, molecular modeling techniques have been used to identify new proteins that can provide a similar fucose binding module in the newly discovered genomic sequences using the above mentioned structural information. We modeled 3-D structures of three such proteins, namely, ebiP5322 protein of Anopheles gambiae, a pentraxin of Xenopus laevis, and the fw gene product of Drosophila melanogaster. alpha-L-fucose was docked in the binding pockets of the modeled structures followed by energy minimization and molecular dynamic runs to obtain the most probable structures of the complexes. Properties of these modeled complexes were studied to examine the nature of physicochemical forces involved in the complex formation and compared with AAA-alpha-L-fucose complex. It was found that ebiP5322 protein of A. gambiae and the pentraxin of X. laevis can provide a fucose-binding fold similar to AAA. We studied structures of four protein-fucose complexes to examine the electrostatic potential surfaces around the binding site and concluded that a highly positive-charged surface was not a necessary condition of fucose-binding.

Animals↗