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Low‐Barrier and Canonical Hydrogen Bonds Modulate Activity and Specificity of a Catalytic Triad
Author(s) -
Kumar Prashasti,
Agarwal Pratul K.,
Waddell M. Brett,
Mittag Tanja,
Serpersu Engin H.,
Cuneo Matthew J.
Publication year - 2019
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201908535
Subject(s) - catalysis , hydrogen bond , catalytic triad , chemistry , low barrier hydrogen bond , hydrogen , active site , acceptor , substrate (aquarium) , hydrogen atom , stereochemistry , chemical physics , photochemistry , crystallography , computational chemistry , molecule , organic chemistry , physics , oceanography , geology , condensed matter physics , alkyl
The position, bonding and dynamics of hydrogen atoms in the catalytic centers of proteins are essential for catalysis. The role of short hydrogen bonds in catalysis has remained highly debated and led to establishment of several distinctive geometrical arrangements of hydrogen atoms vis‐à‐vis the heavier donor and acceptor counterparts, that is, low‐barrier, single‐well or short canonical hydrogen bonds. Here we demonstrate how the position of a hydrogen atom in the catalytic triad of an aminoglycoside inactivating enzyme leads to a thirty‐fold increase in catalytic turnover. A low‐barrier hydrogen bond is present in the enzyme active site for the substrates that are turned over the best, whereas a canonical hydrogen bond is found with the least preferred substrate. This is the first comparison of these hydrogen bonds involving an identical catalytic network, while directly demonstrating how active site electrostatics adapt to the electronic nature of substrates to tune catalysis.