Glucagon structure

TABLE 9.2 Example for energy minimization (geometric optimization). Molecular mechanics energy minimization with Amber is exemplified for geometric optimization of glucagon structure using HyperChem... 

The situation is different for other examples—for example, the peptide hormone glucagon and a small peptide, metallothionein, which binds seven cadmium or zinc atoms. Here large discrepancies were found between the structures determined by x-ray diffraction and NMR methods. The differences in the case of glucagon can be attributed to genuine conformational variability under different experimental conditions, whereas the disagreement in the metallothionein case was later shown to be due to an incorrectly determined x-ray structure. A re-examination of the x-ray data of metallothionein gave a structure very similar to that determined by NMR. 

Most of the G-protein-coupled receptors are homologous with rhodopsin however, other quantitatively minor families as well as some individual receptors do not share any of the structural features common to the rhodopsin family (Figure 2.3). The most dominant of these are the glucagon/VIP/caldtonin receptor family, or family B (which has approximately 65 members), and the metabotropic glutamate receptor family, or family C (which has approximately 15 members), as well as the frizzled/smoothened family of receptors. Thus, the only structural feature that all G-protein-coupled receptors have in common is the seven-transmembrane helical bundle. Nevertheless, most non-rhodopsin-like receptors do have certain minor structural features in common with the rhodopsin-like receptors — for example, a disulfide bridge between the top of TM-III and the middle of extracellular loop-3, and a cluster of basic residues located just below TM-VI. 

Sapse, A.-M., M. Mezei, D. C. Jain, and C. Unson. 1994. Ab Initio Study of Aspartic and Glutamic Acid Supplementary Evidence for Structural Requirements at Postition 9 for Glucagon Activity. J. Mol. Struct. (Theochem) 306, 225-233. 

Traditionally, glucagon preparations utilized therapeutically are chromatographically purified from bovine or porcine pancreatic tissue. (The structure of bovine, porcine and human glucagon is identical, thus eliminating the possibility of direct immunological complications). Such commercial preparations are generally formulated with lactose and sodium chloride and sold in freeze-dried form. Glucagon, 0.5-1.0 units (approximately 0.5-1.0 mg freeze-dried hormone), is administered to the patient by s.c. or i.m. injection. 

Steady-state fluorescence polarization studies have been carried out with a number of peptides, including model peptides, ACTH, glucagon, melittin, and thyrocalcitonin. This work has been reviewed 5 and will not be discussed in the present article. More recently, interesting information on the rotational behavior and structural flexibility of various peptides has been obtained from fluorescence anisotropy decay measurements. 

AC2993/pept. structurally correlated to the human hormone glucagon-like peptide-1... 

R. Iyengar (1986). Structural characterization of the glucagon receptor. In N. Kraus-Friedman (Ed.). Hormonal Control of Gluconeogenesis, vol. 2. Boca Raton CRC Press, pp. 21-34. 

Many other receptors also have a seven-helix structure similar to that of the adrenergic receptors. These include receptors for the following glucagon,... 

Occupied receptors for adrenaline, glucagon, ACTH, and histamine activate adenylate cyclase via Gs proteins. Other Gs proteins, which contain subunits designated aolf and which exist as a number of subtypes, mediate olfactory responses. Subunit aD is another specialized polypeptide which is located primarily in neural tissues. A variety of additional G proteins have been discovered in organisms ranging from bacteria to mammals.179 183-186 All have similar structures with 39- to 45-kDa a subunits, 35- to 36-kDa (3 subunits and 5- to 8-kDa y subunits. Whereas the a subunits are unique to each G protein, (3 and y subunits may be shared among several G proteins. These proteins appear to function with many kinds of hormone receptors and... 

The Coris found that the interconversion of phosphor-ylases a and b is catalyzed by another enzyme, and subsequent work by Earl Sutherland showed that this process is under hormonal control. In muscle, conversion of phosphorylase b to a is stimulated by epinephrine in liver, it is stimulated by both epinephrine and the pancreatic hormone glucagon. The structural basis for the difference between the two forms of phosphorylase remained unknown until the late 1950s, when Edwin Krebs and Edmund Fischer showed that phosphorylase a has a phosphate on serine 14. This phosphate is absent in the b form of the enzyme. Krebs and Fischer also showed that the kinase that catalyzes the addition of the phosphate is itself regulated by a phosphorylation catalyzed by another enzyme, the cAMP-dependent protein kinase ... 

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