Choudhury Susobhan, Batabyal Subrata, Mondal Prasanna Kumar, Singh Priya, Lemmens Peter, Pal Samir Kumar
Department of Chemical, Biological and Macromolecular Sciences, S. N. Bose National Centre for Basic Sciences, Block JD, Sector III, Salt Lake, Kolkata 700 098 (India).
Institute for Condensed Matter Physics and Laboratory for Emergent, Nanometrology, TU Braunschweig, Mendelssohnstrasse 3, 38106 Braunschweig (Germany).
Chemistry. 2015 Nov 2;21(45):16172-7. doi: 10.1002/chem.201501616. Epub 2015 Sep 14.
The pathways of molecular recognition, which is a central event in all biological processes, belong to the most important subjects of contemporary research in biomolecular science. By using fluorescence spectroscopy in a microfluidics channel, it can be determined that molecular recognition of α-chymotrypsin in hydrous surroundings at two different pH values (3.6 and 6.3) follows two distinctly different pathways. Whereas one corroborates an induced-fit model (pH 3.6), the other one (pH 6.3) is consistent with the selected-fit model of biomolecular recognition. The role of massive structural perturbations of differential recognition pathways could be ruled out by earlier XRD studies, rather was consistent with the femtosecond-resolved observation of dynamic flexibility of the protein at different pH values. At low concentrations of ligands, the selected-fit model dominates, whereas increasing the ligand concentration leads to the induced-fit model. From molecular modelling and experimental results, the timescale associated with the conformational flexibility of the protein plays a key role in the selection of a pathway in biomolecular recognition.
分子识别是所有生物过程中的核心事件，其相关途径属于生物分子科学当代研究的最重要课题。通过在微流控通道中使用荧光光谱法，可以确定在两种不同pH值（3.6和6.3）的含水环境中，α-胰凝乳蛋白酶的分子识别遵循两种截然不同的途径。其中一种证实了诱导契合模型（pH 3.6），另一种（pH 6.3）则与生物分子识别的选择契合模型一致。早期的X射线衍射（XRD）研究可以排除差异识别途径中大规模结构扰动的作用，这与在不同pH值下对蛋白质动态柔韧性的飞秒分辨观察结果一致。在低浓度配体时，选择契合模型占主导，而增加配体浓度则导致诱导契合模型。从分子建模和实验结果来看，与蛋白质构象柔韧性相关的时间尺度在生物分子识别途径的选择中起着关键作用。
