TY  - JOUR
AU  - Michalczyk, Ryszard
AU  - Unkefer, Clifford J.
AU  - Bacik, John-Paul
AU  - Schrader, Tobias E.
AU  - Ostermann, Andreas
AU  - Kovalevsky, Andrey Y.
AU  - McKenna, Robert
AU  - Fisher, Suzanne Zoë
TI  - Joint neutron crystallographic and NMR solution studies of Tyr residue ionization and hydrogen bonding: Implications for enzyme-mediated proton transfer
JO  - Proceedings of the National Academy of Sciences of the United States of America
VL  - 112
IS  - 18
SN  - 1091-6490
CY  - Washington, DC
PB  - National Acad. of Sciences
M1  - FZJ-2015-06690
SP  - 5673 - 5678
PY  - 2015
AB  - Proton transfer is a fundamental mechanism at the core of many enzyme-catalyzed reactions. It is also exquisitely sensitive to a number of factors, including pH, electrostatics, proper active-site geometry, and chemistry. Carbonic anhydrase has evolved a fast and efficient way to conduct protons through a combination of hydrophilic amino acid side chains that coordinate a highly ordered H-bonded water network. This study uses a powerful approach, combining NMR solution studies with neutron protein crystallography, to determine the effect of pH and divalent cations on key residues involved in proton transfer in human carbonic anhydrase. The results have broad implications for our understanding of proton transfer and how subtle changes in ionization and H-bonding interactions can modulate enzyme catalysis.
LB  - PUB:(DE-HGF)16
UR  - <Go to ISI:>//WOS:000353953800049
DO  - DOI:10.1073/pnas.1502255112
UR  - https://juser.fz-juelich.de/record/276225
ER  -