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

Michalczyk, Ryszard; Unkefer, Clifford J.; Bacik, John -Paul; Schrader, Tobias E.; Ostermann, Andreas; Kovalevsky, Andrey Y.; McKenna, Robert; Fisher, Suzanne Zoe

doi:10.1073/pnas.1502255112

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

Journal Article · Tue May 05 00:00:00 EDT 2015 · Proceedings of the National Academy of Sciences of the United States of America

DOI:https://doi.org/10.1073/pnas.1502255112· OSTI ID:1236701

Michalczyk, Ryszard ^[1]; Unkefer, Clifford J. ^[1]; Bacik, John -Paul ^[1]; Schrader, Tobias E. ^[2]; Ostermann, Andreas ^[3]; Kovalevsky, Andrey Y. ^[4]; McKenna, Robert ^[5]; Fisher, Suzanne Zoe ^[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)
Technische Univ. Munchen, Garching (Germany)
Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
Univ. of Florida, Gainesville, FL (United States)
Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Julich Centre for Neutron Science (JCNS) at Heinz Maier-Leibnitz Zentrum (MLZ), Garching (Germany)

Human carbonic anhydrase II (HCA II) uses a Zn-bound OH^-/H₂O mechanism to catalyze the reversible hydration of CO₂. This catalysis also involves a separate proton transfer step, mediated by an ordered solvent network coordinated by hydrophilic residues. One of these residues, Tyr7, was previously shown to be deprotonated in the neutron crystal structure at pH 10. This observation indicated that Tyr7 has a perturbed pK_a compared with free tyrosine. To further probe the pK_a) of this residue, NMR spectroscopic measurements of [¹³C] Tyr-labeled holo HCA II (with active-site Zn present) were preformed to titrate all Tyr residues between pH 5.4-11.0. In addition, neutron studies of apo HCA II (with Zn removed from the active site) at pH 7.5 and holo HCA II at pH 6 were conducted. This detailed interrogation of tyrosines in HCA II by NMR and neutron crystallography revealed a significantly lowered pK_a of Tyr7 and how pH and Tyr proximity to Zn affect hydrogen-bonding interactions.

View Accepted Manuscript (DOE)

Cite

Export

Save

Research Organization:: Los Alamos National Laboratory (LANL), Los Alamos, NM (United States); Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Biological and Environmental Research (BER)

Grant/Contract Number:: AC52-06NA25396; AC05-00OR22725; 20110535ER

OSTI ID:: 1236701

Alternate ID(s):: OSTI ID: 1261433

Report Number(s):: LA-UR-15-20968

Journal Information:: Proceedings of the National Academy of Sciences of the United States of America, Vol. 112, Issue 18; ISSN 0027-8424

Publisher:: National Academy of Sciences, Washington, DC (United States)Copyright Statement

Country of Publication:: United States

Language:: English

Citation Metrics:

Cited by: 28 works

Citation information provided by
Web of Science

References (31)

Physiological Functions of the Alpha Class of Carbonic Anhydrases Frost, Susan C. Carbonic Anhydrase: Mechanism, Regulation, Links to Disease, and Industrial Applications https://doi.org/10.1007/978-94-007-7359-2_2	book	September 2013
The catalytic mechanism of carbonic anhydrase: implications of a rate-limiting protolysis of water Silverman, David N.; Lindskog, Sven Accounts of Chemical Research, Vol. 21, Issue 1 https://doi.org/10.1021/ar00145a005	journal	January 1988
Neutron Structure of Human Carbonic Anhydrase II: A Hydrogen-Bonded Water Network “Switch” Is Observed between pH 7.8 and 10.0 Fisher, Zoë; Kovalevsky, Andrey Y.; Mustyakimov, Marat Biochemistry, Vol. 50, Issue 44 https://doi.org/10.1021/bi201487b	journal	November 2011
Protonation and Reactivity towards Carbon Dioxide of the Mononuclear Tetrahedral Zinc and Cobalt Hydroxide Complexes, [Tp ^Bu ^{^{^t} ^,Me ]ZnOH and [Tp ^Bu ^{^{^t} ^,Me ]CoOH: Comparison of the Reactivity of the Metal Hydroxide Function in Synthetic Analogues of Carbonic Anhydrase}} Bergquist, Catherine; Fillebeen, Tauqir; Morlok, Melissa M. Journal of the American Chemical Society, Vol. 125, Issue 20 https://doi.org/10.1021/ja034711j	journal	May 2003
Atomic Crystal and Molecular Dynamics Simulation Structures of Human Carbonic Anhydrase II: Insights into the Proton Transfer Mechanism ^† ^, ^‡ Fisher, S. Zoë; Maupin, C. Mark; Budayova-Spano, Monika Biochemistry, Vol. 46, Issue 11 https://doi.org/10.1021/bi062066y	journal	March 2007
A Short, Strong Hydrogen Bond in the Active Site of Human Carbonic Anhydrase II Avvaru, Balendu Sankara; Kim, Chae Un; Sippel, Katherine H. Biochemistry, Vol. 49, Issue 2 https://doi.org/10.1021/bi902007b	journal	January 2010
Solvent-Mediated Proton Transfer in Catalysis by Carbonic Anhydrase Silverman, David N.; McKenna, Robert Accounts of Chemical Research, Vol. 40, Issue 8 https://doi.org/10.1021/ar7000588	journal	August 2007
Role of histidine 64 in the catalytic mechanism of human carbonic anhydrase II studied with a site-specific mutant Tu, Chingkuang; Silverman, David N.; Forsman, Cecilia Biochemistry, Vol. 28, Issue 19 https://doi.org/10.1021/bi00445a054	journal	September 1989
Tautomerism of Histidine 64 Associated with Proton Transfer in Catalysis of Carbonic Anhydrase Shimahara, Hideto; Yoshida, Takuya; Shibata, Yasutaka Journal of Biological Chemistry, Vol. 282, Issue 13 https://doi.org/10.1074/jbc.M609679200	journal	January 2007
Structural and Kinetic Characterization of Active-Site Histidine as a Proton Shuttle in Catalysis by Human Carbonic Anhydrase II ^† ^, ^‡ Fisher, Zoë; Hernandez Prada, Jose A.; Tu, Chingkuang Biochemistry, Vol. 44, Issue 4 https://doi.org/10.1021/bi0480279	journal	February 2005
Speeding Up Proton Transfer in a Fast Enzyme: Kinetic and Crystallographic Studies on the Effect of Hydrophobic Amino Acid Substitutions in the Active Site of Human Carbonic Anhydrase II ^† Fisher, S. Zoë; Tu, Chingkuang; Bhatt, Deepa Biochemistry, Vol. 46, Issue 12 https://doi.org/10.1021/bi602620k	journal	March 2007
Effect of Active-site Mutation at Asn67 on the Proton Transfer Mechanism of Human Carbonic Anhydrase II Maupin, C. Mark; Zheng, Jiayin; Tu, Chingkuang Biochemistry, Vol. 48, Issue 33 https://doi.org/10.1021/bi901037u	journal	August 2009
Kinetic and crystallographic studies of the role of tyrosine 7 in the active site of human carbonic anhydrase II Mikulski, Rose; Avvaru, Balendu Sankara; Tu, Chingkuang Archives of Biochemistry and Biophysics, Vol. 506, Issue 2 https://doi.org/10.1016/j.abb.2010.12.004	journal	February 2011
Generalized X-ray and neutron crystallographic analysis: more accurate and complete structures for biological macromolecules Adams, Paul D.; Mustyakimov, Marat; Afonine, Pavel V. Acta Crystallographica Section D Biological Crystallography, Vol. 65, Issue 6 https://doi.org/10.1107/S0907444909011548	journal	May 2009
Seeing the chemistry in biology with neutron crystallography Langan, Paul; Chen, Julian C. -H. Physical Chemistry Chemical Physics, Vol. 15, Issue 33 https://doi.org/10.1039/c3cp51760h	journal	January 2013
pK values of the ionizable groups of proteins Thurlkill, Richard L.; Grimsley, Gerald R.; Scholtz, J. Martin Protein Science, Vol. 15, Issue 5 https://doi.org/10.1110/ps.051840806	journal	May 2006
A summary of the measured p K values of the ionizable groups in folded proteins Grimsley, Gerald R.; Scholtz, J. Martin; Pace, C. Nick Protein Science https://doi.org/10.1002/pro.19	journal	January 2008
pH Dependence of the Photoactive Yellow Protein Photocycle Recovery Reaction Reveals a New Late Photocycle Intermediate with a Deprotonated Chromophore Hendriks, Johnny; Hellingwerf, Klaas J. Journal of Biological Chemistry, Vol. 284, Issue 8 https://doi.org/10.1074/jbc.M805904200	journal	December 2008
Structure, dynamics, and ionization equilibria of the tyrosine residues in Bacillus circulans xylanase Baturin, Simon J.; Okon, Mark; McIntosh, Lawrence P. Journal of Biomolecular NMR, Vol. 51, Issue 3 https://doi.org/10.1007/s10858-011-9564-7	journal	September 2011
pKa measurements from nuclear magnetic resonance of tyrosine-150 in class C beta-lactamase Kato-Toma, Yoko; Iwashita, Takashi; Masuda, Katsuyoshi Biochemical Journal, Vol. 371, Issue 1 https://doi.org/10.1042/bj20021447	journal	April 2003
Quantitative dissection of hydrogen bond-mediated proton transfer in the ketosteroid isomerase active site Sigala, P. A.; Fafarman, A. T.; Schwans, J. P. Proceedings of the National Academy of Sciences, Vol. 110, Issue 28 https://doi.org/10.1073/pnas.1302191110	journal	June 2013
Proton Transfer in Carbonic Anhydrase Is Controlled by Electrostatics Rather than the Orientation of the Acceptor ^† Riccardi, Demian; König, Peter; Guo, Hua Biochemistry, Vol. 47, Issue 8 https://doi.org/10.1021/bi701950j	journal	February 2008
Structural properties of human carbonic anhydrase II at pH 9.5 Nair, Satish K.; Christianson, David W. Biochemical and Biophysical Research Communications, Vol. 181, Issue 2 https://doi.org/10.1016/0006-291X(91)91229-6	journal	December 1991
Preferred Orientations of His64 in Human Carbonic Anhydrase II ^† Maupin, C. Mark; Voth, Gregory A. Biochemistry, Vol. 46, Issue 11 https://doi.org/10.1021/bi062170f	journal	March 2007
Entrapment of Carbon Dioxide in the Active Site of Carbonic Anhydrase II Domsic, John F.; Avvaru, Balendu Sankara; Kim, Chae Un Journal of Biological Chemistry, Vol. 283, Issue 45 https://doi.org/10.1074/jbc.M805353200	journal	September 2008
Carbon-13 nuclear magnetic resonance study of tyrosine titrations Norton, Raymond S.; Bradbury, J. Howard Journal of the Chemical Society, Chemical Communications, Issue 21 https://doi.org/10.1039/c3974000870b	journal	January 1974
Comprehensive Determination of Protein Tyrosine pKa Values for Photoactive Yellow Protein Using Indirect 13C NMR Spectroscopy Oktaviani, Nur Alia; Pool, Trijntje J.; Kamikubo, Hironari Biophysical Journal, Vol. 102, Issue 3 https://doi.org/10.1016/j.bpj.2011.12.024	journal	February 2012
Exogenous Sphingosine-1-Phosphate Boosts Acclimatization in Rats Exposed to Acute Hypobaric Hypoxia: Assessment of Haematological and Metabolic Effects Chawla, Sonam; Rahar, Babita; Singh, Mrinalini PLoS ONE, Vol. 9, Issue 6 https://doi.org/10.1371/journal.pone.0098025	journal	June 2014
“Proton Holes” in Long-Range Proton Transfer Reactions in Solution and Enzymes: A Theoretical Analysis Riccardi, Demian; König, Peter; Prat-Resina, Xavier Journal of the American Chemical Society, Vol. 128, Issue 50 https://doi.org/10.1021/ja065451j	journal	December 2006
Proton Transfer Dependence on Hydrogen-Bonding of Solvent to the Water Wire: A Theoretical Study Mai, Binh Khanh; Park, Kisoo; Duong, My Phu Thi The Journal of Physical Chemistry B, Vol. 117, Issue 1 https://doi.org/10.1021/jp310724g	journal	December 2012
Characterizing the Use of Perdeuteration in NMR Studies of Large Proteins:13C,15N and1H Assignments of Human Carbonic Anhydrase II Venters, Ronald A.; Farmer II, Bennett T.; Fierke, Carol A. Journal of Molecular Biology, Vol. 264, Issue 5 https://doi.org/10.1006/jmbi.1996.0699	journal	December 1996

Cited By (7)

Conformational exchange of aromatic side chains by 1H CPMG relaxation dispersion Raum, Heiner N.; Dreydoppel, Matthias; Weininger, Ulrich Journal of Biomolecular NMR, Vol. 72, Issue 1-2 https://doi.org/10.1007/s10858-018-0210-5	journal	September 2018
Thermodynamic, kinetic, and structural parameterization of human carbonic anhydrase interactions toward enhanced inhibitor design Linkuvienė, Vaida; Zubrienė, Asta; Manakova, Elena Quarterly Reviews of Biophysics, Vol. 51 https://doi.org/10.1017/s0033583518000082	journal	January 2018
Exploration of the residues modulating the catalytic features of human carbonic anhydrase XIII by a site-specific mutagenesis approach De Simone, Giuseppina; Di Fiore, Anna; Truppo, Emanuela Journal of Enzyme Inhibition and Medicinal Chemistry, Vol. 34, Issue 1 https://doi.org/10.1080/14756366.2019.1653290	journal	January 2019
Carbonic Anhydrases: Role in pH Control and Cancer Mboge, Mam; Mahon, Brian; McKenna, Robert Metabolites, Vol. 8, Issue 1 https://doi.org/10.3390/metabo8010019	journal	February 2018
Neutron Crystallography for the Study of Hydrogen Bonds in Macromolecules Oksanen, Esko; Chen, Julian C. -H.; Fisher, Suzanne Zoë Molecules, Vol. 22, Issue 4 https://doi.org/10.3390/molecules22040596	journal	April 2017
Thermodynamic, kinetic, and structural parameterization of human carbonic anhydrase interactions toward enhanced inhibitor design Linkuvienė, Vaida; Zubrienė, Asta; Manakova, Elena Deutsches Elektronen-Synchrotron, DESY, Hamburg https://doi.org/10.3204/pubdb-2018-05504	text	January 2018
Insights into the binding mode of sulphamates and sulphamides to hCA II: crystallographic studies and binding free energy calculations De Simone, Giuseppina; Langella, Emma; Esposito, Davide Journal of Enzyme Inhibition and Medicinal Chemistry, Vol. 32, Issue 1 https://doi.org/10.1080/14756366.2017.1349764	journal	January 2017

Similar Records

Production and X-ray crystallographic analysis of fully deuterated human carbonic anhydrase II

Journal Article · Sun Jan 01 00:00:00 EST 2006 · Acta Crystallographica. Section F · OSTI ID:1236701

Budayova-Spano, Monika; Fisher, S. Zoë; Dauvergne, Marie-Thérèse; +4 more

Enzymes for carbon sequestration: neutron crystallographic studies of carbonic anhydrase

Journal Article · Mon Nov 01 00:00:00 EDT 2010 · Acta Crystallographica. Section D: Biological Crystallography · OSTI ID:1236701

Kovalevsky, A. Y.; Domsic, J.; Mustyakimov, M.; +3 more

Effects of tyrosine-26 and tyrosine-64 nitration on the photoreactions of bacteriorhodopsin

Journal Article · Tue Dec 17 00:00:00 EST 1985 · Biochemistry; (United States) · OSTI ID:1236701

Scherrer, P; Stoeckenius, W

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
crystallography
NMR spectroscopy
proton transfer
neutron crystallography
perturbed pKa
solution NMR
37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
36 MATERIALS SCIENCE

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

Citation Formats

References (31)

Cited By (7)

Similar Records

Related Subjects