Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Insulin, glucagon, somatostatin-14, and three structurally related molecular forms of peptide tyrosine-tyrosine (PYY) were isolated from an extract of the combined pancreas and gastrointestinal tract of the pallid sturgeon, Scaphirhynchus albus. Pallid sturgeon insulin was identical to insulin from the Russian sturgeon, Acipenser guldenstaedti, and to insulin-2 from the paddlefish, Polyodon spathula, and was approximately twofold less potent than human insulin in inhibiting the binding of [3-[(125)I] iodotyrosine-A14] human insulin to the soluble human insulin receptor. The sturgeon glucagon (HSQGMFTNDY(10)-SKYLEEKLAQ(20) EFVEWLKNGK(30)S), like the two paddlefish glucagons, contains 31 rather than 29 amino acid residues, indicative of an anomalous pathway of posttranslational processing of proglucagon. Pallid sturgeon somatostatin, identical to human somatostatin-14, was also isolated in a second molecular form containing an oxidized tryptophan residue, but [Pro(2)]somatostatin-14, previously isolated from the pituitary of A. guldenstaedti, was not identified. Sturgeon PYY (FPPKPEHPGD(10)DAPAEDVAKY(20)YTALRHYINL(30) ITRQRY.HN(2)) was also isolated in variant forms containing the substitutions (Phe(1) --> Ala) and (Ala(18) --> Val), indicative of at least two gene duplications occurring within the Acipenseriformes lineage. The amino acid sequences of the pallidsturgeon PYY peptides are appreciably different from the proposed "ancestral" PYY sequence that has otherwise been very strongly conserved among the actinopterygian and elasmobranch fish.
 ...
PMID:Gastroenteropancreatic hormones (insulin, glucagon, somatostatin, and multiple forms of PYY) from the pallid sturgeon, Scaphirhynchus albus (Acipenseriformes). 1112

Time-resolved fluorescence study of single tryptophan-containing proteins, nuclease, ribonuclease T1, protein G, glucagon, and mastoparan, has been carried out. Three different methods were used for the analysis of fluorescence decays: the iterative reconvolution method, as reviewed and developed in our laboratory, the maximum entropy method, and the recent method that we called "energy transfer" method. All the proteins show heterogeneous fluorescence kinetics (multiexponential decay). The origin of this heterogeneity is interpreted in terms of current theories of electron transfer process, which treat the electron transfer process as a radiationless transition. The theoretical electron transfer rate was calculated assuming the peptide bond carbonyl as the acceptor site. The good agreement between experimental and theoretical electron-transfer rates leads us to suggest that the electron-transfer process is the principal quenching mechanism of Trp fluorescence in proteins, resulting in heterogeneous fluorescence kinetics. Furthermore, the origin of apparent homogeneous fluorescence kinetics (monoexponential decay) in some proteins also can be explained on the basis of electron-transfer mechanism.
 ...
PMID:On the involvement of electron transfer reactions in the fluorescence decay kinetics heterogeneity of proteins. 1156 1

Exendin-4, a 39 amino acid peptide originally isolated from the oral secretions of the lizard Heloderma suspectum, has been shown to share certain activities with glucagon-like-peptide-1 (GLP-1), a 30 amino acid peptide. We have determined the structuring preferences of exendin-4 and GLP-1 by NMR in both the solution and dodecylphosphocholine (DPC) micelle-associated states. Based on both chemical shift deviations and the pattern of intermediate range NOEs, both peptides display significant helicity from residue 7 to residue 28 with greater fraying at the N-terminus. Thornton and Gorenstein [(1994) Biochemistry 33, 3532-3539] reported that the presence of a flexible, helix-destabilizing, glycine at residue 16 in GLP-1 was an important feature for membrane and receptor binding. Exendin-4 has a helix-favoring glutamate as residue 16. In the micelle-associated state, NMR data indicate that GLP-1 is less helical than exendin-4 due to the presence of Gly16; chemical shift deviations along the peptide sequence suggest that Gly16 serves as an N-cap for a second, more persistent, helix. In 30 vol-% trifluoroethanol (TFE), a single continuous helix is evident in a significant fraction of the GLP-1 conformers present. Exendin-4 has a more regular and less fluxional helix in both media and displays stable tertiary structure in the solution state. In the micelle-bound state of exendin-4, a single helix (residues 11-27) is observed with residues 31-39 completely disordered and undergoing rapid segmental motion. In aqueous fluoroalcohol or aqueous glycol, the Leu21-Pro38 span of exendin-4 forms a compact tertiary fold (the Trp-cage) which shields the side chain of Trp25 from solvent exposure and produces ring current shifts as large as 3 ppm. This tertiary structure is partially populated in water and fully populated in aqueous TFE. The Leu21-Pro38 segment of exendin-4 may be the smallest protein-like folding unit observed to date. When the Trp-cage forms, fraying of the exendin-4 helix occurs exclusively from the N-terminus; backbone NHs for the C-terminal residues of the helix display H/D exchange protection factors as large as 10(5) at 9 degrees C. In contrast, no tertiary structure is evident when exendin-4 binds to DPC micelles. An energetically favorable insertion of the tryptophan ring into the DPC micelle is suggested as the basis for this change. With the exception of exendin-4 in media containing fluoro alcohol cosolvents, NMR structure ensembles generated from the NOE data do not fully reflect the conformational averaging present in these systems. Secondary structure definition from chemical shift deviations may be the most appropriate treatment for peptides that lack tertiary structure.
 ...
PMID:Exendin-4 and glucagon-like-peptide-1: NMR structural comparisons in the solution and micelle-associated states. 1168 27

A cDNA clone encoding a cysteine proteinase of the papain superfamily has been isolated from the hepatopancreas of northern shrimp Pandalus borealis (NsCys). NsCys shares the highest identity of 64% with a cathepsin L-like cysteine proteinase from lobster, and its identity to the well-characterized mammalian cathepsins S, L, and K falls within a narrow range of 54-59%. However, it differs from each of these cathepsins in certain key residues including, for example, the unique occurrence of tryptophan and cysteine residues at the structurally important S2 subsite. Consequently, NsCys produced in Pichia pastoris appears to be distinct in various physicokinetic properties. The recombinant enzyme is active and stable over a wide range of pH values, and its substrate specificity is unusual, as demonstrated by its poor affinity for phenylalanine residues. Instead, it shows the highest specificity for proline residues, a property similar to cathepsin K. Unlike cathepsin K, however, NsCys cleaves valine residues more efficiently than leucine. Similar results were obtained with the natural peptide substrate glucagon. The shrimp proteinase is further distinguished by its potent collagenolytic activity, resulting in a cleavage pattern reminiscent of bacterial collagenase. To distinguish such unique structural and enzymatic properties, we propose the trivial name "crustapain" for the shrimp proteinase, indicating that it is a papain-like cysteine proteinase from a crustacean species.
 ...
PMID:Molecular cloning and functional characterization of crustapain: a distinct cysteine proteinase with unique substrate specificity from northern shrimp Pandalus borealis. 1286 37

Plant proteins have a reduced content of essential amino acids in comparison to animal proteins. A significant reduction of limiting amino acids (methionine, lysine, tryptophan) means lower protein synthesis. In subjects with predominant or exclusive consumption of plant food a higher incidence of hypoproteinemia due to significant reduction of methionine and lysine intakes was observed. On the other hand, lower intake of these amino acids provides a preventive effect against cardiovascular disease via cholesterol regulation by an inhibited hepatic phospholipid metabolism. Vegetarians have a significantly higher intake of non-essential amino acids arginine and pyruvigenic amino acids glycine, alanine, serine. When plant protein is high in non-essential amino acids, down-regulation of insulin and up-regulation of glucagon is a logical consequence. The action of glucagon in the liver is mediated by stimulation of adenyl cyclase that raises cyclic-AMP (adenosine-3,5-monophosphate) concentrations. Cyclic-AMP down-regulates the synthesis of a number of enzymes required for de novo lipogenesis and cholesterol synthesis, up-regulates key gluconeogenic enzymes and the LDL receptors and decreases the IGF-1 activity (insulin-like growth factor). Cyclic-AMP thus provides a reduction of atherosclerosis risk factors as well as a retardation of cancer development. A sufficient consumption of plant proteins has the protective effects against chronic degenerative diseases (Tab. 2, Ref. 26).
 ...
PMID:Health benefits and risks of plant proteins. 1620 43

The biosynthesis of glucagon was studied by using the recirculated, isolated perfused rat pancreas. [(3)H]Tryptophan was initially incorporated into acid-ethanol-extractable protein, which on gel filtration was eluted with a molecular weight of about 9000 and contained a small amount of glucagon immunoreactivity. With longer incubation [(3)H]tryptophan incorporation into a second peak was obtained in an identical position with that of the majority of rat glucagon immunoreactivity. This peak of labelled protein exhibited migration characteristics on polyacrylamide-gel electrophoresis identical with those of rat glucagon and was identified as newly synthesized glucagon by demonstration of specific binding and dissociation behaviour with glucagon antibodies. The incorporation of [(3)H]tryptophan into acid-ethanol-extractable protein was inhibited by cycloheximide. High concentrations of glucose increased [(3)H]tryptophan incorporation into high-molecular-weight protein but decreased incorporation into proteins smaller than cytochrome c. The pattern of [(3)H]leucine incorporation into protein was similar to that of [(3)H]tryptophan.
 ...
PMID:The biosynthesis of glucagon in perfused rat pancreas. 1674 7

The corticotropin-releasing factor (CRF) receptors, CRF-R1 and CRF-R2, belong to the B1 subfamily of G protein-coupled Receptors (GPCRs), including receptors for secretin, growth hormone-releasing hormone (GHRH), vasoactive intestinal peptide (VIP), pituitary adenylate cyclase-activating polypeptide (PACAP), calcitonin, parathyroid hormone (PTH), glucagon, and glucagon-like peptide-1 (GLP-1). The peptide ligand family comprises CRF, Ucn 1, 2, and 3. CRF plays the major role in integrating the response to stress. Additionally, the ligands exhibit many effects on muscle, pancreas, heart, and the GI, reproductive, and immune systems. CRF-R1 has higher affinity for CRF than does CRF-R2 while both receptors bind Ucn 1 equally. CRF-R2 shows specificity for Ucns 2 and 3. A major binding domain of the CRFRs is the N terminus/first extracellular domain (ECD1). Soluble proteins corresponding to the ECD1s of each receptor bind CRF ligands with nanomolar affinities. Our three-dimensional (3D) nuclear magnetic resonance (NMR) structure of a soluble protein corresponding to the ECD1 of CRF-R2beta (1) identified its structural fold as a Sushi domain/short consensus repeat (SCR), stabilized by three disulfide bridges, two tryptophan residues, and an internal salt bridge (Asp65-Arg101). Disruption of the bridge by D65A mutation abrogates ligand recognition and results in loss of the well-defined disulfide pattern and Sushi domain structure. NMR analysis of the ECD1 in complex with astressin identified key amino acids involved in ligand recognition. Mutation of some of these residues in the full-length receptor reduces its affinity for CRF ligands. A structure-based sequence comparison shows conservation of key amino acids in all the B1 subfamily receptors, suggesting a corresponding conservation of a Sushi domain structural fold of their ECD1s.
 ...
PMID:The three-dimensional structure of the N-terminal domain of corticotropin-releasing factor receptors: sushi domains and the B1 family of G protein-coupled receptors. 1688 52

Recent work suggests that the molecular structure of amyloid-like fibrils is determined by environmental conditions as well as amino acid sequence. To probe the involvement of side chains in fibrillation of the 29-residue hormone glucagon, we have measured fibrillation kinetics of 15 alanine mutants. At acidic pH, all of the mutants are able to form fibrils. However, substitution of hydrophobic residues in the N- and C-termini (in particular Phe6, Tyr10, Val23, and Met27) decelerates fibrillation dramatically. This indicates that the hydrophobicity and/or high beta-sheet propensity of these residues may be important for fibrillation. In contrast, substitution of Leu14 increases fibrillation propensity compared to that of the wild type. Nevertheless, despite identical fibrillation conditions, the thioflavin T and tryptophan fluorescence spectra of fibrils formed by mutants Tyr13, Leu14, and Asp15 are significantly different from those of other mutants, indicating that substitution of these residues may influence not only the fibrillation kinetics and fibril stability but also the preferred final structure of the fibrils that is formed, in line with the general structural polymorphism of glucagon fibrils. In contrast, under alkaline conditions, only a handful of the alanine mutants are capable of forming fibrils, suggesting that more side chains are involved in stabilizing interactions here. In addition, fibrils formed by wild-type glucagon at alkaline pH appear very stable, compared to fibrils formed at acidic pH. This suggests that the distribution of charges determines the number of different fibrillated states available to a peptide, since these can block formation of metastable fibrillated states.
 ...
PMID:N- and C-terminal hydrophobic patches are involved in fibrillation of glucagon. 1712 89

The physical stability and the secondary structure of a glucagon-like peptide-1 derivative were investigated in the presence of the metal ions Al(3+), Zn(2+), Mg(2+), and K(+), known as possible leachables from container-closure systems. Metal ions were investigated in concentrations of 0-50 ppm. Test solutions of the peptide were exposed to elevated temperature (25 degrees C) and rotation (37 degrees C) for up to 4 weeks. The samples were examined by nephelometry, thioflavine T fluorescence, and Fourier-transform infrared spectroscopy. Readily prepared test solutions were examined by tryptophan fluorescence. The stability profiles were unchanged after addition of Mg(2+) and K(+) in 0-50 ppm concentrations. However, a concentration-dependent increase in thioflavine intensities was observed after addition of Al(3+) and Zn(2+). The destabilising effect of Al(3+) and Zn(2+) was furthermore confirmed by FTIR as the secondary structure of the peptide changed from predominantly alpha-helix to a higher beta-sheet content. Additionally Al(3+) changed the secondary structure of the peptide using Trp fluorescence.
 ...
PMID:Preliminary studies of the physical stability of a glucagon-like peptide-1 derivate in the presence of metal ions. 1719 2

Glucagon selectively potentiates an effect of hydrocortisone: when injected into adrenalectoinized rats it increases fourfold the induction by hydrocortisone of tyrosine transaminase, but not of tryptophan pyrrolase. Glucagon alone doubles the basal level of tyrosine transaminase and decreases that of tryptophan pyrrolase. The effects of glucagon on both enzymes resemble those of starvation.
 ...
PMID:Glucagon, starvation, and the induction of liver enzymes by hydrocortisone. 1782 69


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