Cowsik S M, Lücke C, Rüterjans H
School of Life Sciences, Jawaharlal Nehru University, New Delhi, India.
J Biomol Struct Dyn. 1997 Aug;15(1):27-36. doi: 10.1080/07391102.1997.10508942.
Both the aqueous and the lipid-induced structure of a representative and widely studied tachykinin, substance P, has been investigated by two-dimensional proton nuclear magnetic resonance (2D 1H-NMR) spectroscopy and distance geometry calculations. Unambiguous NMR assignments of protons have been made with the aid of correlation spectroscopy (COSY and TOCSY) experiments and Overhauser enhancement spectroscopy (ROESY and NOESY; experiments. The NMR data obtained were utilized in a distance geometry algorithm to generate a family of structures which were further refined using restrained energy minimization. These data show that, while in water substance P appears to favour an extended chain conformation, in the presence of perdeuterated dodecylphosphocholine (DPC) micelles as membrane model system an amphiphilic helical conformation is induced in the mid-region (Q5-Q8) of substance P. The conformation adopted by substance P in the presence of DPC micelles yields a structural motif typical of neurokinin-1 selective ligands, as proposed by Convert and coworkers (O. Convert et al., Neuropeptides 19, 259-270 (1991)).
一种具有代表性且被广泛研究的速激肽——P物质,其在水溶液和脂质诱导下的结构均已通过二维质子核磁共振(2D 1H-NMR)光谱法和距离几何计算进行了研究。借助相关光谱(COSY和TOCSY)实验以及奥弗豪泽效应增强光谱(ROESY和NOESY)实验,已对质子进行了明确的核磁共振归属。将获得的核磁共振数据用于距离几何算法,以生成一系列结构,再使用受限能量最小化对其进行进一步优化。这些数据表明,P物质在水中似乎倾向于伸展链构象,而在作为膜模型系统的全氘代十二烷基磷酰胆碱(DPC)胶束存在的情况下,P物质的中间区域(Q5-Q8)会诱导出两亲性螺旋构象。正如Convert及其同事所提出的(O. Convert等人,《神经肽》19,259-270(1991)),P物质在DPC胶束存在时所采用的构象产生了一种典型的神经激肽-1选择性配体的结构基序。