Uroshlev L A, Torshin I Iu, Batianovskiĭ A V, Esipova N G, Tumanian V G
Biofizika. 2015 Jan-Feb;60(1):5-14.
The work presents the results of an exhaustive conformational analysis of β-turns involving amino acid residues with disallowed backbone conformation of the polypeptide chain. It is known that the first residue of the β-turn (Asn47) of the distal β-hairpin in the α-spectrin SH3-domain is characterized by sterically disallowed main chain conformation (values of the dihedral angles (φ and ψ are in the right bottom quadrant of the Ramachandran plot). All α-spectrin structures with the anomalous elements deposited in the PDB were analysed. We hypothesized that the formation of disallowed conformation may occur through the fixation (due to the SH3 domain structure) of the adjacent to the β-turn amino acid residues with the β-structure. These residues are disposed in such a manner that β-turn conformation of the residues contributes just to the disallowed local conformation of this residue whereas any other β-turn conformations (with allowed local conformation) are impossible. To test this hypothesis an exhaustive conformational analysis of the β-bend has been performed by altering internal coordinates (two pairs of φ and ψ angles and two Ω angles). The conformations were selected as a result of grid search procedure with. 1 degrees step that corresponded to stereochemically allowed local deformations of the polypeptide chain segment forming the β-turn. In all conformations obtained the local conformation of Asn47 rests in the disallowed region. The conformations found include conformations coinciding with experimentally determined structures from the PDB as well as an additional variant that differs from X-ray structure in values of a pair of φ and ψ angles of the second residue belonging to the β-bend. Values of these angles fall in the region of the Ramachandran plot near the line φ = 0 (and negative values of ψ) i.e. in strongly disallowed region without experimental points. Therefore the additional variants of the β-turn local deformation are impossible to observe in experiment. Thus, the idea that disallowed conformation is intruded to the β-bend by fixation of adjacent residues receives confirmation in this work. The topological limitations in a context of the structure in such kind of β-hairpins exclude the allowed local conformations.
这项工作展示了对涉及多肽链主链构象不允许的氨基酸残基的β-转角进行详尽构象分析的结果。已知α-血影蛋白SH3结构域中远端β-发夹的β-转角的第一个残基（Asn47）的特征是主链构象在空间上不被允许（二面角（φ和ψ）的值位于拉氏图的右下方象限）。对PDB中所有带有异常元件的α-血影蛋白结构进行了分析。我们推测，不被允许的构象的形成可能是由于（由于SH3结构域结构）与β-转角相邻的氨基酸残基被固定为β-结构。这些残基的排列方式使得这些残基的β-转角构象恰好导致该残基的不被允许的局部构象，而任何其他β-转角构象（具有允许的局部构象）是不可能的。为了验证这一假设，通过改变内部坐标（两对φ和ψ角以及两个Ω角）对β-弯曲进行了详尽的构象分析。这些构象是通过网格搜索程序以1度步长选择的，这对应于形成β-转角的多肽链片段的立体化学允许的局部变形。在获得的所有构象中，Asn47的局部构象都位于不被允许的区域。找到的构象包括与PDB中实验确定的结构一致的构象，以及一种额外的变体，该变体在属于β-弯曲的第二个残基的一对φ和ψ角的值上与X射线结构不同。这些角度的值落在拉氏图中靠近φ = 0线（以及ψ的负值）的区域，即在没有实验点的强烈不被允许的区域。因此，在实验中不可能观察到β-转角局部变形的额外变体。因此，不被允许的构象通过相邻残基的固定侵入到β-弯曲中的观点在这项工作中得到了证实。在这种β-发夹结构的背景下的拓扑限制排除了允许的局部构象。
