Perczel A, Fasman G D
Graduate Department of Biochemistry, Brandeis University, Waltham, Massachusetts 02254-9110.
Protein Sci. 1992 Mar;1(3):378-95. doi: 10.1002/pro.5560010310.
The beta-turn is a frequently found structural unit in the conformation of globular proteins. Although the circular dichroism (CD) spectra of the alpha-helix and beta-pleated sheet are well defined, there remains some ambiguity concerning the pure component CD spectra of the different types of beta-turns. Recently, it has been reported (Hollósi, M., Kövér, K.E., Holly, S., Radics, L., & Fasman, G.D., 1987, Biopolymers 26, 1527-1572; Perczel, A., Hollósi, M., Foxman, B.M., & Fasman, G.D., 1991a, J. Am. Chem. Soc. 113, 9772-9784) that some pseudohexapeptides (e.g., the cyclo[(delta)Ava-Gly-Pro-Aaa-Gly] where Aaa = Ser, Ser(OtBu), or Gly) in many solvents adopt a conformational mixture of type I and the type II beta-turns, although the X-ray-determined conformation was an ideal type I beta-turn. In addition to these pseudohexapeptides, conformational analysis was also carried out on three pseudotetrapeptides and three pseudooctapeptides. The target of the conformation analysis reported herein was to determine whether the ring stress of the above beta-turn models has an influence on their conformational properties. Quantitative nuclear Overhauser effect (NOE) measurements yielded interproton distances. The conformational average distances so obtained were interpreted utilizing molecular dynamics (MD) simulations to yield the conformational percentages. These conformational ratios were correlated with the conformational weights obtained by quantitative CD analysis of the same compounds. The pure component CD curves of type I and type II beta-turns were also obtained, using a recently developed algorithm (Perczel, A., Tusnády, G., Hollósi, M., & Fasman, G.D., 1991b, Protein Eng. 4(6), 669-679). For the first time the results of a CD deconvolution, based on the CD spectra of 14 beta-turn models, were assigned by quantitative NOE results. The NOE experiments confirmed the ratios of the component curves found for the two major beta-turns by CD analysis. These results can now be used to enhance the conformational determination of globular proteins on the basis of their CD spectra.
β-转角是球状蛋白质构象中常见的结构单元。虽然α-螺旋和β-折叠片的圆二色性（CD）光谱已明确，但不同类型β-转角的纯组分CD光谱仍存在一些不明确之处。最近有报道（霍洛西，M.，科韦尔，K.E.，霍利，S.，拉迪克斯，L.，& 法斯曼，G.D.，1987年，《生物聚合物》26卷，1527 - 1572页；佩尔采尔，A.，霍洛西，M.，福克斯曼，B.M.，& 法斯曼，G.D.，1991a年，《美国化学会志》113卷，9772 - 9784页）称，一些假六肽（如环[（δ）Ava - Gly - Pro - Aaa - Gly]，其中Aaa = Ser、Ser（OtBu）或Gly）在许多溶剂中呈现I型和II型β-转角的构象混合物，尽管X射线测定的构象是理想的I型β-转角。除了这些假六肽，还对三种假四肽和三种假八肽进行了构象分析。本文报道的构象分析目标是确定上述β-转角模型的环张力是否对其构象性质有影响。定量核Overhauser效应（NOE）测量得出质子间距离。利用分子动力学（MD）模拟对如此获得的构象平均距离进行解释，以得出构象百分比。这些构象比例与通过对相同化合物进行定量CD分析获得的构象权重相关。还使用最近开发的算法（佩尔采尔，A.，图斯纳迪，G.，霍洛西，M.，& 法斯曼，G.D.，1991b年，《蛋白质工程》4（6）卷，669 - 679页）获得了I型和II型β-转角的纯组分CD曲线。首次根据14种β-转角模型的CD光谱进行的CD去卷积结果，由定量NOE结果进行了赋值。NOE实验证实了通过CD分析在两种主要β-转角中发现的组分曲线比例。这些结果现在可用于在基于球状蛋白质CD光谱的基础上加强其构象测定。
