Mantha Anil K, Chandrashekar Indu R, Baquer Najma Z, Cowsik Sudha M
School of Life Sciences, Jawaharlal Nehru University, New Delhi--110 067, India.
J Biomol Struct Dyn. 2004 Oct;22(2):137-48. doi: 10.1080/07391102.2004.10506990.
Neurokinin B (NKB), a decapeptide of mammalian origin exhibits a variety of biological activities such as regulatory functions in reproduction, pre-eclampsia and neuroprotection in Alzheimer's disease. In order to gain insight into structure-function relationship, three-dimensional structure of NKB has been investigated using CD spectropolarimetry and two-dimensional proton nuclear magnetic resonance (2D 1H-NMR) spectroscopy in aqueous and membrane mimetic solvents. Unambiguous NMR assignments of resonances have been made with the aid of correlation spectroscopy (DQF-COSY and TOCSY) experiments and Nuclear Overhauser Effect Spectroscopy (NOESY) experiments. Distance constraints obtained from the NMR data have been used to generate a family of structures, which have been refined using restrained energy minimization and dynamics. Our data show that a helical structure is induced in NKB, in presence of perdeuterated dodecyl phosphocholine (DPC) micelles, a membrane model system. Further, the conformation adopted by NKB in presence of DPC micelles represents a structural motif typical of neurokinin-3 selective agonists.
神经激肽B（NKB）是一种源自哺乳动物的十肽，具有多种生物活性，如在生殖、先兆子痫中的调节功能以及对阿尔茨海默病的神经保护作用。为了深入了解结构 - 功能关系，已在水性和膜模拟溶剂中使用圆二色光谱法（CD）和二维质子核磁共振（2D 1H-NMR）光谱法研究了NKB的三维结构。借助相关光谱实验（双量子滤波相关谱（DQF-COSY）和全相关谱（TOCSY））以及核Overhauser效应光谱实验（NOESY），对共振进行了明确的核磁共振归属。从核磁共振数据获得的距离约束已用于生成一系列结构，并使用受限能量最小化和动力学对其进行了优化。我们的数据表明，在膜模型系统全氘代十二烷基磷酸胆碱（DPC）胶束存在下，NKB会诱导形成螺旋结构。此外，NKB在DPC胶束存在下所采用的构象代表了神经激肽-3选择性激动剂典型的结构基序。
