Kumar Thakur A, Venugopalan P, Kishore R
Institute of Microbial Technology, Sector 39-A, Chandigarh-, 160 036, India.
Biochem Biophys Res Commun. 2000 Jul 5;273(2):492-8. doi: 10.1006/bbrc.2000.2966.
The single-crystal X-ray diffraction analysis of a nonchiral beta-Ala-containing model peptide, Boc-beta-Ala-Aib-OCH(3) 1 (beta-Ala, 3-aminopropionic acid; Aib, alpha-aminoisobutyric acid), establishes the coexistence of distinctly different backbone conformations in two crystallographically independent molecules, A and B, in the asymmetric unit. Interestingly, the central mu torsion angle around the -C(beta)-C(alpha)- bond of the conformationally flexible beta-Ala residue appears to be critical in dictating the overall distinct structural features, i.e., in molecule A it adopts a folded gauche conformation: mu = -71.0 degrees, whereas it favors an extended trans conformation, mu = 161.2 degrees, in molecule B. As expected, the stereochemically constrained Aib residue preferred an energetically favorable folded backbone conformation, the torsion angles being phi = 46.2 degrees and psi = 48.3 degrees for molecule A and phi = -43.6 degrees and psi = -45.5 degrees for molecule B, lying in the left-handed and right-handed helical regions of the Ramachandran map, respectively. Considering the signs as well as the magnitudes of the backbone torsional angles, molecule A typically folds into a pseudo type III' beta-turn-like structure while molecule B prefers an overall extended conformation. Entrapping the two dramatically distinct conformational characteristics in the crystalline state clearly suggests that the gauche and the trans effects of the beta-Ala moieties are indeed energetically accessible to a short linear peptide and receive strong experimental support. The analyses permitted us to emphasize that in addition to conformational constraints of the neighboring residue, the chemical nature of the side-chain acyclic substituents and the "local environments" collectively seem to influence the stabilization of the folding-unfolding behavior of the two methylene units (-CONH-CH(2)-CH(2)-CONH-) in 1.
对一种不含手性的含β-丙氨酸的模型肽Boc-β-丙氨酸-α-氨基异丁酸甲酯1（β-丙氨酸即3-氨基丙酸；α-氨基异丁酸即Aib）进行的单晶X射线衍射分析表明，在不对称单元中两个晶体学独立的分子A和B中存在明显不同的主链构象共存。有趣的是，构象灵活的β-丙氨酸残基围绕-C(β)-C(α)-键的中心μ扭转角似乎在决定整体独特的结构特征方面起着关键作用，即，在分子A中它采用折叠的 gauche构象：μ = -71.0°，而在分子B中它倾向于伸展的反式构象，μ = 161.2°。正如所预期的，立体化学受限的Aib残基更喜欢能量上有利的折叠主链构象，对于分子A，扭转角为φ = 46.2°和ψ = 48.3°，对于分子B，扭转角为φ = -43.6°和ψ = -45.5°，分别位于拉氏图的左手螺旋区和右手螺旋区。考虑到主链扭转角的符号和大小，分子A通常折叠成类似假III'型β-转角的结构，而分子B更喜欢整体伸展的构象。在晶体状态下捕获这两种截然不同的构象特征清楚地表明，β-丙氨酸部分的gauche效应和反式效应对于短线性肽在能量上确实是可及的，并得到了有力的实验支持。这些分析使我们能够强调，除了相邻残基的构象限制外，侧链无环取代基的化学性质和“局部环境”似乎共同影响了1中两个亚甲基单元（-CONH-CH₂-CH₂-CONH-）折叠-展开行为的稳定性。
