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Title: Joint neutron crystallographic and NMR solution studies of Tyr residue ionization and hydrogen bonding: Implications for enzyme-mediated proton transfer

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. Lastly, 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.
Authors:
 [1] ;  [1] ;  [1] ;  [2] ;  [3] ;  [4] ;  [5] ;  [6]
  1. Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
  2. Julich Centre for Neutron Science (JCNS) at Heinz Maier-Leibnitz Zentrum (MLZ), Garching (Germany)
  3. Technische Univ. Munchen, Garching (Germany)
  4. Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
  5. Univ. of Florida, Gainesville, FL (United States)
  6. Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Julich Centre for Neutron Science (JCNS) at Heinz Maier-Leibnitz Zentrum (MLZ), Garching (Germany)
Publication Date:
OSTI Identifier:
1236701
Report Number(s):
LA-UR--15-20968
Journal ID: ISSN 0027-8424
Grant/Contract Number:
AC52-06NA25396
Type:
Accepted Manuscript
Journal Name:
Proceedings of the National Academy of Sciences of the United States of America
Additional Journal Information:
Journal Volume: 112; Journal Issue: 18; Journal ID: ISSN 0027-8424
Publisher:
National Academy of Sciences, Washington, DC (United States)
Research Org:
Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
Sponsoring Org:
USDOE
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES crystallography; NMR spectroscopy; proton transfer; neutron crystallography; perturbed pKa; solution NMR