Melanocortins, which are involved in melanocyte pigmentation control and glucocorticoid stimulation, have functional roles in various physiological mechanisms and have been shown to participate in higher cortical functions. Recently, it has also been reported that melanocyte-stimulating hormone (MSH) and melanocortin 4 receptor (MC4R) are the key components of the hypothalamic response to obesity. The solution structures of both melanocyte-stimulating hormone α-MSH (Ac-Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2) and its analog α-MSH-ND (Ac-Ahx-Asp-His-DPhe-Arg-Trp-Lys-NH2) (Ahx, 2- aminohexanoic acid) have been determined by two-dimensional NMR spectroscopy and simulated-annealing calculations. The NMR data revealed that α-MSH forms a hairpin loop conformation which includes conserved message sequences, whereas α-MSH-ND prefers a type I β-turn comprising residues of Asp2-His3- DPhe4-Arg5. Final simulated-annealing structures of both α-MSH-ND and α- MSH peptides converged with rmsd of 0.07 nm for α-MSH-ND and 0.1 nm for α- MSH between backbone atoms, respectively This result will provide the structural bases of melanocortin functions as well as valuable information for structure-based drug design involving the regulation of obesity and feeding.
|Number of pages
|European Journal of Biochemistry
|Published - 1998 Oct 1
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