Solution structures of the melanocyte-stimulating hormones by two-dimensional NMR spectroscopy and dynamical simulated-annealing calculations.
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 alpha-MSH (Ac-Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2) and its analog alpha-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 alpha-MSH forms a hairpin loop conformation which includes conserved message sequences, whereas alpha-MSH-ND prefers a type I beta-turn comprising residues of Asp2-His3-DPhe4-Arg5. Final simulated-annealing structures of both alpha-MSH-ND and alpha-MSH peptides converged with rmsd of 0.07 nm for alpha-MSH-ND and 0.1 nm for alpha-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.
Lee
J H
JH
Department of Biochemistry, College of Science, Yonsei University, Seoul, Korea.
Lim
S K
SK
Huh
S H
SH
Lee
D
D
Lee
W
W
D000595:Amino Acid Sequence; D009682:Magnetic Resonance Spectroscopy; D009074:Melanocyte-Stimulating Hormones / Q000737:chemistry*; D008958:Models, Molecular; D017433:Protein Structure, Secondary
D009074:Melanocyte-Stimulating Hormones