Glucagon, conformation

Glucagon Conformation in Different Environments Implications for Molecular Recognition... 

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. 

Deduce the probable conformation of porcine glucagon with the following sequence (construct initial structure in a helix from amino acids with HyperChem which lists residue ID in PDB file) by geometry optimization until the difference in energies between the successive steps is less than 1.0 kcal/mol or rms gradient of 0.1 kcal/(mol-A) ... 

Glucagon is a 29-residue hormone whose primary biological role is to stimulate glucose release and production. In dilute aqueous solution the peptide is in a random conformation, but it can be induced to adopt a largely helical conformation under a variety of conditions. Under basic conditions it aggregates to form an a-helical trimer, and the crystal structure of this trimer is known (Sasaki et al., 1975). It also adopts a partially helical conformation when it forms mixed micelles with detergents (Braun et al., 1983). 

W. Braun, C. Bosch. L. R. Brown, N. Go, and K. Wiithrich, Biochim. Biophys. Acta, 667, 377 (1981). Combined Use of Proton-Proton Overhauser Enhancements and a Distance Geometry Algorithm for Determination of Polypeptide Conformations. Application to Micelle-Bound Glucagon. 

Senderoff RI, Kontor KM, Kreilgaard L, ChangJJ, Patel S, KrakavorJ, Heffeman JK, Snell LB, and Rosenberg GB. Consideration of Conformations and Racem-ization during Process Development of Recombinant Glucagon-like Peptide-1. 

Another effect of glucagon binding to liver cells is the inactivation of the glycolytic enzyme pyruvate kinase. (Protein kinase C, an enzyme activated by cAMP, converts pyruvate kinase to its inactive phosphorylated conformation.) Hormones also influence gluconeogenesis by altering enzyme synthesis. For example, the synthesis of gluconeogenic enzymes is stimulated by cortisol (a steroid hormone... 

The function of heterotrimeric G proteins is illustrated in Figure 11.17 using a hormone that activates adenylyl cyclase (e.g., glucagon or epinephrine). While the a subunit contains bound GDP, it remains associated with the (3 and y subunits, either free in the membrane or bound to an unoccupied receptor (see Fig. 11.17, part 1). When the hormone binds, it causes a conformational change in the receptor that activates GDP dissociation and GTP binding. The exchange of GTP for bound GDP causes dissociation of the a subunit from the receptor and from the (3y subunits (see Fig. 11.17, part 2). The a and (3 subunits are tethered to the intracellular side of the... 

Somatostatin [somatotropin release inhibiting factor (SRIF), Ala-Gly-cyclo(Cys-Lys-Asn-Phe-Phe-Trp-Lys-Thr-Phe-Thr-Ser-Cys)] is a hypothalamic hormone that inhibits the release of growth hormone, insulin, and glucagon. Somatostatin is believed to adopt an overall p-sheet conformation with a... 

Senderoff, R.I. Kontor, K.M. Kreilgaard, L. Chang, J.J. Patel, S. Krakover, J. Heffeman, J.K. Snell, L.B. Rosenberg, G.B. Consideration of conformational transitions and racemization during process development of recombinant glucagon-like peptide-1. J. Pharm. Sci. 1998, 87, 183-189. 

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