Novotny Marian, Kleywegt Gerard J
Department of Cell and Molecular Biology, Uppsala University, Box 596, SE-751 24 Uppsala, Sweden.
J Mol Biol. 2005 Mar 25;347(2):231-41. doi: 10.1016/j.jmb.2005.01.037.
All naturally occurring amino acids with the exception of glycine contain one or more chiral carbon atoms and can therefore occur in two different configurations, L (levo, left-handed) and D (dextro, right-handed). Proteins are almost exclusively built from L-amino acids. The stereochemical bias of nature is further reflected at the secondary structure level where right-handed helices are strongly preferred over left-handed helices. The handedness of helices has not received much attention in the past and is often overlooked during the analysis, description and deposition of experimentally solved protein structures. Therefore, an extensive survey of left-handed helices in the Protein Data Bank (PDB) was undertaken to analyse their frequency of occurrence, length, amino acid composition, conservation and possible structural or functional role. All left-handed helices (of four or more residues) in a non-redundant subset of the PDB, were identified using hydrogen-bonding analysis, comparison of related structures, and experimental electron density assessment to filter out likely spurious and artefactual hits. This analysis yielded 31 verified left-handed helices in a set of 7284 proteins. The phi angles of the residues in the left-handed helices lie between 30 degrees and 130 degrees and the psi angles lie between -50 degrees and 100 degrees . Most of the helices are short (four residues) and for 87% of them, it was possible to determine that they are important for the stability of the protein, for ligand binding, or as part of the active site. This suggests that, even though left-handed helices are rare, when they do occur, they are structurally or functionally significant. Four secondary structure assignment programs were tested for their ability to identify the handedness of the helices. Of these programs, only DSSP correctly assigns the handedness.
除甘氨酸外，所有天然存在的氨基酸都含有一个或多个手性碳原子，因此可以以两种不同的构型存在，即L型（左旋，左手性）和D型（右旋，右手性）。蛋白质几乎完全由L型氨基酸构成。自然界的这种立体化学偏向在二级结构水平上进一步体现，其中右手螺旋比左手螺旋更受青睐。螺旋的手性在过去没有受到太多关注，在实验解析的蛋白质结构的分析、描述和存档过程中常常被忽视。因此，我们对蛋白质数据库（PDB）中的左手螺旋进行了广泛调查，以分析它们的出现频率、长度、氨基酸组成、保守性以及可能的结构或功能作用。使用氢键分析、相关结构比较和实验电子密度评估，对PDB非冗余子集中所有四个或更多残基的左手螺旋进行识别，以滤除可能的假阳性和人为干扰的命中结果。该分析在7284种蛋白质中产生了31个经过验证的左手螺旋。左手螺旋中残基的φ角在30度至130度之间，ψ角在-50度至100度之间。大多数螺旋较短（四个残基），其中87%的螺旋可以确定它们对蛋白质的稳定性、配体结合或作为活性位点的一部分很重要。这表明，尽管左手螺旋很少见，但当它们出现时，在结构或功能上具有重要意义。测试了四个二级结构分配程序识别螺旋手性的能力。在这些程序中，只有DSSP能正确分配手性。
