Breeze A L, Harvey T S, Bazzo R, Campbell I D
Department of Biochemistry, University of Oxford, U.K.
Biochemistry. 1991 Jan 15;30(2):575-82. doi: 10.1021/bi00216a036.
The structure of human calcitonin gene-related peptide 1 (hCGRP-1) has been determined by 1H NMR in a mixed-solvent system of 50% trifluoroethanol/50% H2O at pH 3.7 and 27 degrees C. Complete resonance assignment was achieved by using two-dimensional methods. Distance restraints for structure calculations were obtained by semiquantitative analysis of intra- and interresidue nuclear Overhauser effects; in addition, stereospecific or X1 rotamer assignments were obtained for certain side chains. Structures were generated from the distance restraints by distance geometry, followed by refinement using molecular dynamics, and were compared with experimental NH-C alpha H coupling constants and amide hydrogen exchange data. The structure of hCGRP-1 in this solvent comprises an amino-terminal disulfide-bonded loop (residues 2-7) leading into a well-defined alpha-helix between residues 8 and 18; thereafter, the structure is predominantly disordered, although there are indications of a preference for a turn-type conformation between residues 19 and 21. Comparison of spectra for the homologous hCGRP-2 with those of hCGRP-1 indicates that the conformations of these two forms are essentially identical.
人降钙素基因相关肽1（hCGRP - 1）的结构已通过1H NMR在pH值为3.7、温度为27℃的50%三氟乙醇/50% H2O混合溶剂体系中测定。通过二维方法实现了完整的共振归属。结构计算的距离约束通过对残基内和残基间核Overhauser效应的半定量分析获得；此外，还获得了某些侧链的立体专一性或X1旋转异构体归属。通过距离几何从距离约束生成结构，随后使用分子动力学进行优化，并与实验性的NH - CαH耦合常数和酰胺氢交换数据进行比较。hCGRP - 1在这种溶剂中的结构包括一个氨基末端二硫键连接的环（残基2 - 7），其后是8至18位残基之间定义明确的α - 螺旋；此后，结构主要是无序的，尽管有迹象表明19至21位残基之间倾向于形成转角型构象。同源的hCGRP - 2与hCGRP - 1的光谱比较表明，这两种形式的构象基本相同。
