Cramer Jonathan, Jiang Xiaohua, Schönemann Wojciech, Silbermann Marleen, Zihlmann Pascal, Siegrist Stefan, Fiege Brigitte, Jakob Roman Peter, Rabbani Said, Maier Timm, Ernst Beat
Institute of Molecular Pharmacy, University of Basel Klingelbergstrasse 50 4056 Basel Switzerland
Institute of Structural Biology, University of Basel Klingelbergstrasse 70 4056 Basel Switzerland.
RSC Chem Biol. 2020 Aug 28;1(4):281-287. doi: 10.1039/d0cb00108b. eCollection 2020 Oct 1.
In biological systems, polar interactions are heavily burdened by high desolvation penalties resulting from strong solute-solvent interactions. As a consequence thereof, enthalpic contributions of hydrogen bonds to the free energy of binding are severely diminished. However, this effect is strongly attenuated for interactions within solvent-shielded areas of proteins. In microcalorimetric experiments, we show that the bacterial lectin FimH utilizes conformational adaptions to effectively shield its binding site from solvent. The transition into a lower dielectric environment results in an enthalpic benefit of approximately -13 kJ mol for mannoside binding. However, this effect can be abrogated, if the hydrogen bond network within the binding site is disturbed by deoxygenation of the ligand. Conformational adaption leading to reduced local dielectric constants could represent a general mechanism for proteins to enable enthalpy-driven recognition of polar ligands.
在生物系统中，极性相互作用因溶质 - 溶剂强相互作用产生的高去溶剂化惩罚而负担沉重。因此，氢键对结合自由能的焓贡献会大幅减少。然而，对于蛋白质溶剂屏蔽区域内的相互作用，这种效应会大大减弱。在微量热实验中，我们表明细菌凝集素FimH利用构象适应来有效保护其结合位点免受溶剂影响。转变到较低介电环境会使甘露糖苷结合产生约 -13 kJ/mol的焓增益。然而，如果结合位点内的氢键网络因配体脱氧而受到干扰，这种效应就会被消除。导致局部介电常数降低的构象适应可能是蛋白质实现焓驱动的极性配体识别的一种普遍机制。
