UMLS:C0027960 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

Query: UMLS:C0027960 (mole)
21,279 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human chorionic gonadotropin (hCG), human luteinizing hormone, human thyroid-stimulating hormone, and human follicle-stimulating hormone are closely related family of proteins which share a common alpha-subunit. However, their sugar moieties are quite different. hCG contains five acidic asparagine-linked sugar chains. These five sugar chains are derived by sialylation from three neutral oligosaccharides: two biantennary (N-1 and N-2) and one monoantennary (N-3) complex-type oligosaccharides. Although hCG purified from the urine of pregnant women is more enriched in sialylated sugar chains than that purified from placenta, the molar ratio of N-1, N-2, and N-3 of these two hCGs are the same (1:2:1). Comparative study of the sugar moieties of the alpha- and beta-subunits of hCG revealed that alpha contains 1 mol each of N-2 and N-3, while beta contains 1 mol each of N-1 and N-2. This specific distribution of oligosaccharides at the four asparagine loci of the hCG molecule is now helping us to consider the functional role of the sugar moiety of glycohormones. hCG is produced not only by the trophoblast but also by various trophoblastic diseases. The hCGs purified from the urine of patients with hydatidiform mole contain the same oligosaccharides as normal hCG. However, those from the urine of choriocarcinoma patients contain five additional neutral oligosaccharides. In contrast, hCGs from invasive-mole patients contain three of the five oligosaccharides, specifically found in choriocarcinoma hCGs. The malignant transformational change of the sugar moiety of hCG can be explained by an increase of a fucosyltransferase, which forms the Fuc alpha 1----6GlcNAc group and by ectopic expression and subsequent modification of N-acetylglucosaminyltransferase IV. The appearance of tumor-specific sugar chains of hCG has been used to develop a new diagnostic method for invasive mole and choriocarcinoma.
...
PMID:Structures, function, and transformational changes of the sugar chains of glycohormones. 283 26

Experiments using equilibrium dialysis and fluorescence quenching provided direct evidence that approximately four moles of L-aspartic acid were bound per mole of tetrameric L-asparaginase from Escherichia coli, with a dissociation constant on the order of 60-160 microM. In addition, a set of weaker binding sites with a dissociation constant in the millimolar range were detected. Kinetic studies also revealed that L-aspartic acid inhibited L-asparaginase competitively, with an inhibition constant of 80 microM at micromolar concentrations of L-asparagine; at millimolar concentrations of the amide, an increase in maximal velocity but a decrease in affinity for L-asparagine were observed. L-Aspartic acid at millimolar levels again displayed competitive inhibition. These and other observations suggest that L-aspartic acid binds not only to the active site but also a second site with lower intrinsic affinity for it. The observed "substrate activation" is most likely attributable to the binding of a second molecule of L-asparagine rather than negative cooperativity among the tight sites of the subunits of this tetrameric enzyme. Further support for L-aspartic acid binding to the active site comes from experiments in which the enzyme, when exposed to various group-specific reagents suffered parallel loss of catalytic activity and in its ability to bind L-aspartic acid. Different commercial preparations of Escherichia coli L-asparaginase were found to contain approximately 2-4 moles of L-aspartic acid; these were incompletely removed by dialysis, but could be removed by transamination or decarboxylation. Efficiency of dialysis increased with increasing pH. Taken together, this set of results is consistent with the existence of a covalent beta-aspartyl enzyme intermediate.
...
PMID:Interaction between L-aspartic acid and L-asparaginase from Escherichia coli: binding and inhibition studies. 333 41

Two naturally occurring non-enzymic glucosylceramide activator proteins (A1a and A1b activator) shown previously to be immunochemically not detectable in a new variant of human Gaucher disease (glucosylceramide lipidosis) without glucosylceramidase deficiency, were characterized by amino-acid sequence and carbohydrate content. The complete amino-acid sequence of the A1a activator was determined. The protein consists of 80 amino-acid residues including three disulfide bridges lacking arginine and tryptophan. The molecular mass is 8.95 kDa. About 20% of the polypeptide chain are shorter by two amino-acid residues at the N-terminal end. The A1b activator was characterized by the amino-acid compositions of all tryptic peptides and of the entire protein; sequencing was performed of the regions 1-34 and 42-56. Identical results were obtained for the polypeptide chains of both A1 activators. This suggests that they do not differ in their primary structures which is in agreement with the immunochemical results. The difference between A1a and A1b activator is due to the carbohydrate part. The total amount of 49% carbohydrate in A1a and 76.7% in A1b consists mainly of hexoses. Both chains contain two moles of N-acetylglucosamine per mole protein bound to asparagine in position 22. A comparison of the primary structure of the A1 activator with the sulfatide activator sequence revealed an interesting similarity, especially of the cysteine residues and the carbohydrate-binding asparagine. Sequence homology was also found between a part of the A1 activator sequence and the hemagglutinin neuraminidase of influenza virus as well as to a hypothetical glycoprotein of the Epstein-Barr virus. The comparison with human lysosomal glucosylcerebrosidase showed no sequence similarity.
...
PMID:Complete amino-acid sequence and carbohydrate content of the naturally occurring glucosylceramide activator protein (A1 activator) absent from a new human Gaucher disease variant. 344

Human chorionic gonadotropin (hCG) highly purified from the urine of patients with trophoblastic diseases (choriocarcinoma and hydatidiform mole) and from healthy pregnant women contains four asparagine-linked sugar chains in one molecule. Comparative studies of the sugar chains released by hydrazinolysis revealed that the structures of the sugar chains of choriocarcinoma hCGs are quite different from those of mole and normal hCGs. The carbohydrate structures of mole hCGs are the same as those of normal hCG, while all choriocarcinoma hCGs examined contain two triantennary, two unusual biantennary, and one monoantennary complex-type sugar chains which are not found in normal hCGs. The triantennary and unusual biantennary sugar chains contain the +/- NeuAc alpha 2----Gal beta 1----4GlcNAc beta 1----4Man alpha 1----3 group in common. The total amounts of fucosylated sugar chains in choriocarcinoma hCGs are twice those found in the hCGs of other groups. Therefore, the appearance of the N-acetylglucosaminyl transferase responsible for the formation of the GlcNAc beta 1----4Man alpha 1----3 group and the increase of the fucosyl transferase responsible for the formation of the Fuc alpha 1----6 GlcNAc----Asn group appear to be specific characteristics of malignant transformation of the trophoblast, and the structural changes of sugar chains could serve as useful markers for the diagnosis of choriocarcinoma.
...
PMID:Comparison of carbohydrate structure between human chorionic gonadotropin present in urine of patients with trophoblastic diseases and healthy individuals. 393 Apr 53

The effects of temperature (T), ionic strength (mu), and pH on the polymerization of the coat protein of the E66 strain of tobacco mosaic virus (TMV) from the 4 S form (A), a trimer of the polypeptide chain, to the 20 S form (D) were investigated by the method of sedimentation velocity. Interpretations of thermodynamic parameters were based on only those data obtained in experiments for which reversibility could be demonstrated both by lowering temperature and by lowering concentration. E66 protein differed from vulgare TMV in that, in position 140, lysine replaced asparagine. Thus, E66 protein should be less hydrophobic than vulgare protein and K's, the salting-out constant, should be less. The charge on unpolymerized E66 protein was -3 proton units per polypeptide chain, compared to -4 for vulgare protein. The electrical work contribution, delta W*el, for E66 protein should be (-3/-4)2, or 0.5625 that for vulgare. The results were that delta W*el at pH 6.7, 15 degrees C, and mu = 0.1 was 0.700 kcal/mol for E66 protein compared to 1.22 for vulgare. The experimental ratio was 0.574; K's = 2.16 for E66 compared to 4.93 for vulgare. Hydrogen ions (1.5) were bound per A unit, or 0.5 per polypeptide chain, in the formation of D from A. delta H*, the enthalpy change per mole of A, was 33 kcal at pH 6.7 and 36 at pH 6.9, compared to 30 at both pH values for vulgare protein. delta S*, the entropy change per mole of A, was +132.1 e.u. for E66 compared to 127.4 for vulgare. Entropy-driven processes are found in dynamic biological situations. Ready reversibility at biological temperatures is a requirement, yet the polymer structures must be strong and well ordered. This is achieved through a large number of weak bonds between subunits, combined with ready reversibility under slightly changed conditions. The significant role of water is to facilitate depolymerization by binding to subunits.
...
PMID:Comparison of the entropy-driven polymerization reactions of E66 and vulgare tobacco mosaic virus proteins. 396 3

1. Inhibition of ox liver glutamate dehydrogenase with N-(N'-acetyl-4[(35)S]-sulphamoylphenyl)maleimide (ASPM) is more specific at pH7.3 than at pH6.9. At pH7.3 inhibition accompanies the incorporation at 1 mole of ASPM residues into about 53000g. of protein. 2. Digestion of the modified protein with chymotrypsin and trypsin yields a unique radioactive peptide. 3. Acid hydrolysis of 1 mole of this peptide yields 1 mole of N(in)-succin-2-yl-lysine. The in-amino group of a lysyl residue is thus the site of modification of the protein. 4. The sequence containing the modified lysyl residue is: [Formula: see text] where Asx respresents either aspartic acid or asparagine.
...
PMID:A peptide containing a reactive lysyl group from ox liver glutamate dehydrogenase. 578 69

In cultured melanotic melanoma, a marked decrease of pigmentation has been found to be induced by the addition of tunicamycin [Y. Mishima and G. Imokawa (1983) J. Invest. Dermatol. 81, 106-114]. Since it appears that this impaired pigmentation arises from the loss of asparagine-linked sugar chains serving as a signal for transport of tyrosinase from GERL (Golgi-associated endoplasmic reticulum of lysosomes) to premelanosomes, tyrosinases from the membrane fraction of Greene's hamster melanoma have been purified, and the structures of their sugar chains have been analyzed. Two kinds of tyrosinases were purified by Triton X-100 solubilization; DEAE-cellulose, Sephadex G-200, and DEAE-Sephadex column chromatography; and preparative polyacrylamide gel electrophoresis. The two tyrosinases were separated by polyacrylamide gel electrophoresis, and both corresponded to Mr 69,000. Their asparagine-linked sugar chains were released by hydrazinolysis and analyzed. The sugar chains of the two tyrosinases were identical except for the sialic acid contents. One mole of each tyrosinase contained 1 mol of high-mannose-type sugar chains and 3 mol of complex-type sugar chains. The former chain has Man3 approximately 5 X GlcNAc2 and the latter has Man3 X GlcNAc beta 1----4(+/- Fuc alpha 1----6)GlcNAc as their core structures. The complex-type sugar chains are composed of mono-, bi-, tri-, and tetraantennary sugar chains, with +/- Sia alpha 2----3Gal beta 1----4GlcNAc beta 1----as their outer chains.
...
PMID:Purification of hamster melanoma tyrosinases and structural studies of their asparagine-linked sugar chains. 643 39

Adrenal proenkephalin contains the sequence -Asn-Ser-Ser- that is a typical site for the attachment of asparagine-linked carbohydrate. The 5300- and 18,200-Da bovine adrenal proteins derived from proenkephalin contain this recognition sequence and were therefore analyzed for the presence of both amino and neutral sugars. Les than 0.05 mol of amino sugar and less than 0.1 mol of neutral sugar were found per mole of each protein. No amino sugar was detected in other high-molecular-weight adrenal [Met]enkephalin-containing proteins. Together these findings indicate that bovine adrenal proenkephalin does not contain asparagine-linked carbohydrate.
...
PMID:Is adrenal proenkephalin glycosylated? 687 Feb 64

1. Native cGMP-gated channels were studied in rod outer segments of the larval tiger salamander, Ambystoma tigrinum. The alpha-subunit of the cGMP-gated channel, here referred to as the wild type (WT), and mutant channels were heterologously expressed in Xenopus laevis oocytes. These channels were studied in excised membrane patches in the inside-out configuration and were activated by the addition of 100 or 500 microM cGMP. The current carried by monovalent cations was measured under voltage-clamp conditions. 2. In the presence of 110 mM Na+ in the extracellular medium and different amounts of Na+ in the intracellular medium, the I-V relations of the native channel could be described by a single-site model with a profile of Gibbs free energy with two barriers and a well. A similar result was obtained in the presence of 110 mM Li+ in the extracellular medium and different amounts of Li+ in the intracellular medium. The well depth was 1.4RT (where R is the gas constant and T is the absolute temperature) for both Li+ and Na+. 3. The I-V relations of the native channel in the presence of 110 mM Na+ on one side of the membrane and 110 mM Li+ on the other side could not be described by the same single-site model with identical values of barriers and well obtained in the presence of Li+ or Na+ alone: the well for Li+ had to be at least 4RT. 4. In the presence of mixtures of 110 mM Li+ and Cs+ on the cytoplasmic side of the membrane, an anomalous mole fraction effect was observed both in the native and the WT channel. No anomalous behaviour was seen in the presence of Li(+)-Na+ and Li(+)-NH4+ mixtures. 5. The anomalous mole fraction effect with mixtures of Li+ and Cs+ was not observed in the channel where glutamate 363 was mutated to a glutamine (E363Q) or an asparagine (E363N). When glutamate 363 was mutated to an aspartate (E363D), the anomalous mole fraction effect with mixtures of Li+ and Cs+ was still observed, although significantly reduced. 6. When lysine 346, arginine 369, aspartate 370 and glutamate 372 were neutralized by mutation to glutamine, the ion permeation through the mutant channels and the WT channel had largely similar properties.(ABSTRACT TRUNCATED AT 400 WORDS)
...
PMID:The multi-ion nature of the cGMP-gated channel from vertebrate rods. 747 47

CD59 is an 18-kDa glycoprotein widely expressed on human cells. An important structural feature of CD59 is its attachment to the cell surface via a glycosyl-phosphatidylinositol (GPI) anchor. CD59, like many GPI-anchored proteins, has been found in urine, serum, and other body fluids. The structures of the GPI anchor and the asparagine-linked sugar chain of a soluble form of CD59 in urine, U-CD59, were determined. Purified U-CD59 released 1 mol of inositol per mole of protein by nitrous acid deamination, which cleaved between glucosamine and inositol present commonly in the GPI anchor. This indicates that a GPI anchor, which ended with inositol, is linked at the carboxy terminus of U-CD59. The peptide containing an asparagine-linked sugar chain and the peptide containing a glycan portion of the GPI anchor were isolated after trypsin digestion of U-CD59. The asparagine-linked sugar chains and the glycan portion of the GPI anchor were isolated from these peptides following hydrazinolysis or deamination and dephosphorylation, respectively. Their structures were analyzed by sequential exoglycosidase digestion and methylation analyses. The structures of the asparagine-linked sugar chains of U-CD59 were biantennary complex type, only 4.2% of which are monosialylated. The backbone structure of the GPI anchor was similar to that of Try-panosoma brucei variant surface glycoprotein, but showed significant variations in its side-chain moieties. This is the first detailed structural analysis of the human GPI anchor and the first detailed analysis of the carboxyl-terminal structure of the soluble-form GPI-anchored protein. The results indicate that the backbone structure of the GPI anchor is conserved from parasites to human and that at least a part of the soluble-form GPI-anchored protein has the structure produced by the action of glycan-phosphatidylinositol-specific phospholipase D.
...
PMID:Structural study on the glycosyl-phosphatidylinositol anchor and the asparagine-linked sugar chain of a soluble form of CD59 in human urine. 751 86

<< Previous 1 2 3 4 Next >>