Bioinformatics Centre, (Centre of Excellence in Structural Biology and Bio-computing), Indian Institute of Science, Bangalore 560 012, India.
Int J Biol Macromol. 2010 Apr 1;46(3):317-23. doi: 10.1016/j.ijbiomac.2010.01.011. Epub 2010 Jan 25.
It is well established that a sequence template along with the database is a powerful tool for identifying the biological function of proteins. Here, we describe a method for predicting the catalytic nature of certain proteins among the several protein structures deposited in the Protein Data Bank (PDB). For the present study, we considered a catalytic triad template (Ser-His-Asp) found in serine proteases. We found that a geometrically optimized active site template can be used as a highly selective tool for differentiating an active protein among several inactive proteins, based on their Ser-His-Asp interactions. For any protein to be proteolytic in nature, the bond angle between Ser O(gamma)-Ser H(gamma)...His N(epsilon2) in the catalytic triad needs to be between 115 degrees and 140 degrees. The hydrogen bond distance between Ser H(gamma)...His N(epsilon2) is more flexible in nature and it varies from 2.0 A to 2.7 A while in the case of His H(delta1)...Asp O(delta1), it is from 1.6A to 2.0 A. In terms of solvent accessibility, most of the active proteins lie in the range of 10-16 A(2), which enables easy accessibility to the substrate. These observations hold good for most catalytic triads and they can be employed to predict proteolytic nature of these catalytic triads.
已经证实，序列模板和数据库是识别蛋白质生物功能的强大工具。在这里，我们描述了一种预测蛋白质数据库（PDB）中几种蛋白质结构中某些蛋白质催化性质的方法。在本研究中，我们考虑了丝氨酸蛋白酶中发现的催化三联体模板（Ser-His-Asp）。我们发现，基于 Ser-His-Asp 相互作用，经过几何优化的活性位点模板可以用作区分活性蛋白和几种非活性蛋白的高度选择性工具。对于任何具有蛋白水解性质的蛋白质，催化三联体中 Ser O(gamma)-Ser H(gamma)...His N(epsilon2) 的键角需要在 115 度到 140 度之间。Ser H(gamma)...His N(epsilon2) 之间的氢键距离在性质上更加灵活，其范围为 2.0 A 到 2.7 A，而在 His H(delta1)...Asp O(delta1) 的情况下，其范围为 1.6A 到 2.0 A。就溶剂可及性而言，大多数活性蛋白位于 10-16 A(2)的范围内，这使其能够轻松接近底物。这些观察结果适用于大多数催化三联体，可以用于预测这些催化三联体的蛋白水解性质。
