IAM   02674
INSTITUTO ARGENTINO DE MATEMATICA ALBERTO CALDERON
Unidad Ejecutora - UE
artículos
Título:
Packing defects functionalize soluble proteins
Autor/es:
ARIEL FERNANDEZ
Revista:
FEBS LETTERS
Editorial:
ELSEVIER SCIENCE BV
Referencias:
Lugar: Amsterdam; Año: 2015 vol. 589 p. 967 - 967
ISSN:
0014-5793
Resumen:
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.2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.