Sindic Caleb M T, Muiño Pedro L, Callis Patrik R
Montana State University, Chemistry and Biochemistry Building, PO Box 173400, Bozeman, Montana 59717, United States.
Department of Chemistry, Saint Francis University, PO Box 600, Loretto, Pennsylvania 15940, United States.
ACS Omega. 2025 Apr 28;10(18):18419-18427. doi: 10.1021/acsomega.4c10721. eCollection 2025 May 13.
Despite the demonstrable dependence of enzyme functionality on solvation, the notion of water being directly chemically required for catalysis inside active sites remains unexplored. Here we report that over 99% of 1013 enzyme crystals obtained by X-ray crystallography with high resolution (<1.5 Å) contain continuous chains of water linking residues within the active site to bulk water. Also reported are the findings which inspired this study-that electric fields experienced by water hydrogen atoms are on average twice as strong in the active sites of both chains of bacterial polynucleotide kinase (PDB 4QM6) structures compared to those in bulk water. These results point to the possibility that water molecules within active sites may be paramount to the immense catalytic power of enzymes, especially for mechanisms requiring hydronium or hydroxide ions.
尽管酶的功能明显依赖于溶剂化作用，但关于活性位点内部催化作用直接需要水进行化学反应这一概念仍未得到探索。在此我们报告，通过高分辨率（<1.5 Å）X射线晶体学获得的1013个酶晶体中，超过99%含有将活性位点内的残基与大量水相连的连续水链。本文还报告了启发本研究的发现——细菌多核苷酸激酶（PDB 4QM6）结构两条链的活性位点中，水分子氢原子所经历的电场强度平均是大量水中的两倍。这些结果表明，活性位点内的水分子对于酶的巨大催化能力可能至关重要，特别是对于需要水合氢离子或氢氧根离子的机制而言。
