Lee J H, Lim S K, Huh S H, Lee D, Lee W
Department of Biochemistry, College of Science, Yonsei University, Seoul, Korea.
Eur J Biochem. 1998 Oct 1;257(1):31-40. doi: 10.1046/j.1432-1327.1998.2570031.x.
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.
促黑素细胞激素参与黑素细胞色素沉着控制和糖皮质激素刺激，在多种生理机制中发挥功能作用，并已被证明参与高级皮质功能。最近，也有报道称促黑素细胞激素（MSH）和促黑素皮质素4受体（MC4R）是下丘脑对肥胖反应的关键组成部分。促黑素细胞激素α-MSH（Ac-Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2）及其类似物α-MSH-ND（Ac-Ahx-Asp-His-DPhe-Arg-Trp-Lys-NH2）（Ahx，2-氨基己酸）的溶液结构已通过二维核磁共振光谱和模拟退火计算确定。核磁共振数据显示，α-MSH形成一个发夹环构象，其中包括保守的信息序列，而α-MSH-ND更喜欢由Asp2-His3-DPhe4-Arg5残基组成的I型β-转角。α-MSH-ND和α-MSH肽的最终模拟退火结构分别在主链原子之间收敛，α-MSH-ND的均方根偏差为0.07 nm，α-MSH的均方根偏差为0.1 nm。这一结果将为促黑素皮质素功能提供结构基础，并为涉及肥胖和进食调节的基于结构的药物设计提供有价值的信息。
