Packing defects functionalize soluble proteins

作者：Fernandez Ariel^*

来源：FEBS LETTERS, 2015, 589(9): 967-973.

DOI：10.1016/j.febslet.2015.03.002

• Soluble protein
• Structural biology
• Molecular biophysics
• Packing defect
• Enzyme catalysis
• Catalytic stimulation

This work explores the participation of protein packing defects, the so-called dehydrons, in biochemical events. We delineate the enabling role of dehydrons as activators of nucleophilic groups. This activation results from the induction of chemical basicity in interfacial water molecules, promoting deprotonation of adjacent nucleophiles. Through multiple steering molecular dynamics with pulling along the proton-displacement coordinate, we show that nucleophilic groups are functionally enabled by nearby dehydrons that promote proton transference. The computations are validated against experimentally determined pKa decreases at functional sites and biochemical probes of deregulated catalytic activity arising from dehydron-generating mutations.

• 出版日期2015-4-13