Solvent Entropy Contributions to Catalytic Activity in Designed and Optimized Kemp Eliminases

Belsare, Saurabh; Pattni, Viren; Heyden, Matthias; Head-Gordon, Teresa

doi:10.1021/acs.jpcb.7b07526

Title: Solvent Entropy Contributions to Catalytic Activity in Designed and Optimized Kemp Eliminases

Journal Article · Tue Sep 12 00:00:00 EDT 2017 · Journal of Physical Chemistry. B, Condensed Matter, Materials, Surfaces, Interfaces and Biophysical Chemistry

DOI:https://doi.org/10.1021/acs.jpcb.7b07526· OSTI ID:1532319

Belsare, Saurabh ^[1]; Pattni, Viren ^[2];

^[2];

^[3]

Univ. of California, Berkeley, CA (United States)
Max-Planck-Institut fur Kohlenforschung (Germany)
Univ. of California, Berkeley, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

This work reports on the role of solvation for enzymatic catalysis in two distinct, artificially designed Kemp Eliminases, KE07 and KE70, and mutated variants that were optimized by laboratory directed evolution. Using a spatially resolved analysis of hydration patterns, intermolecular vibrations, and local solvent entropies, we identify distinct classes of hydration water and follow their changes upon substrate binding and transition state formation for the designed KE07 and KE70 enzymes and their evolved variants. We observe that differences in hydration of the enzymatic systems are concentrated in the active site and undergo significant changes during substrate recruitment. For KE07, directed evolution reduces variations in the hydration of the polar catalytic center upon substrate binding, preserving strong protein-water interactions, while the evolved enzyme variant of KE70 features a more hydrophobic reaction center for which the expulsion of low-entropy water molecules upon substrate binding is substantially enhanced. While our analysis suggests a system-dependent role of solvation for the substrate binding process, we identify more subtle changes in solvation for the transition state formation, which are less affected by directed evolution.

View Accepted Manuscript (DOE)

Cite

Export

Save

Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES); German Research Foundation (DFG)

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1532319

Journal Information:: Journal of Physical Chemistry. B, Condensed Matter, Materials, Surfaces, Interfaces and Biophysical Chemistry, Vol. 122, Issue 21; ISSN 1520-6106

Publisher:: American Chemical SocietyCopyright Statement

Country of Publication:: United States

Language:: English

Citation Metrics:

Cited by: 11 works

Citation information provided by
Web of Science

References (33)

Mechanism of Chorismate Mutase: Contribution of Conformational Restriction to Catalysis in the Claisen Rearrangement Khanjin, Nikolai A.; Snyder, James P.; Menger, F. M. Journal of the American Chemical Society, Vol. 121, Issue 50 https://doi.org/10.1021/ja992453d	journal	December 1999
Electrostatic Basis for Enzyme Catalysis Warshel, Arieh; Sharma, Pankaz K.; Kato, Mitsunori Chemical Reviews, Vol. 106, Issue 8 https://doi.org/10.1021/cr0503106	journal	August 2006
The Importance of the Scaffold for de Novo Enzymes: A Case Study with Kemp Eliminase Bhowmick, Asmit; Sharma, Sudhir C.; Head-Gordon, Teresa Journal of the American Chemical Society, Vol. 139, Issue 16 https://doi.org/10.1021/jacs.6b12265	journal	April 2017
Bulk-solvent and hydration-shell fluctuations, similar to - and -fluctuations in glasses, control protein motions and functions Fenimore, P. W.; Frauenfelder, H.; McMahon, B. H. Proceedings of the National Academy of Sciences, Vol. 101, Issue 40 https://doi.org/10.1073/pnas.0405573101	journal	September 2004
Protein folding is slaved to solvent motions Frauenfelder, H.; Fenimore, P. W.; Chen, G. Proceedings of the National Academy of Sciences, Vol. 103, Issue 42 https://doi.org/10.1073/pnas.0607168103	journal	October 2006
Hydration Water Dynamics Near Biological Interfaces Johnson, Margaret E.; Malardier-Jugroot, Cecile; Murarka, Rajesh K. The Journal of Physical Chemistry B, Vol. 113, Issue 13 https://doi.org/10.1021/jp806183v	journal	December 2008
Hydration Dynamics Near a Model Protein Surface Russo, Daniela; Hura, Greg; Head-Gordon, Teresa Biophysical Journal, Vol. 86, Issue 3 https://doi.org/10.1016/S0006-3495(04)74252-6	journal	March 2004
Role of Water in Stabilizing Ferricyanide Trianion and Ion-Induced Effects to the Hydrogen-Bonding Water Network at Long Distance DiTucci, Matthew J.; Heiles, Sven; Williams, Evan R. Journal of the American Chemical Society, Vol. 137, Issue 4 https://doi.org/10.1021/ja5119545	journal	January 2015
An extended dynamical hydration shell around proteins Ebbinghaus, S.; Kim, S. J.; Heyden, M. Proceedings of the National Academy of Sciences, Vol. 104, Issue 52 https://doi.org/10.1073/pnas.0709207104	journal	December 2007
The role of side chain entropy and mutual information for improving the de novo design of Kemp eliminases KE07 and KE70 Bhowmick, Asmit; Sharma, Sudhir C.; Honma, Hallie Physical Chemistry Chemical Physics, Vol. 18, Issue 28 https://doi.org/10.1039/C6CP03622H	journal	January 2016
Evaluation and ranking of enzyme designs: Evaluation and Ranking of Enzyme Designs Kiss, Gert; Röthlisberger, Daniela; Baker, David Protein Science, Vol. 19, Issue 9 https://doi.org/10.1002/pro.462	journal	July 2010
The two-phase model for calculating thermodynamic properties of liquids from molecular dynamics: Validation for the phase diagram of Lennard-Jones fluids Lin, Shiang-Tai; Blanco, Mario; Goddard, William A. The Journal of Chemical Physics, Vol. 119, Issue 22 https://doi.org/10.1063/1.1624057	journal	December 2003
Two-Phase Thermodynamic Model for Efficient and Accurate Absolute Entropy of Water from Molecular Dynamics Simulations Lin, Shiang-Tai; Maiti, Prabal K.; Goddard, William A. The Journal of Physical Chemistry B, Vol. 114, Issue 24 https://doi.org/10.1021/jp103120q	journal	June 2010
Distinct Protein Hydration Water Species Defined by Spatially Resolved Spectra of Intermolecular Vibrations Pattni, Viren; Vasilevskaya, Tatiana; Thiel, Walter The Journal of Physical Chemistry B, Vol. 121, Issue 31 https://doi.org/10.1021/acs.jpcb.7b03966	journal	July 2017
Thermodynamic Properties of a Rigid‐Sphere Fluid Carnahan, Norman F.; Starling, Kenneth E. The Journal of Chemical Physics, Vol. 53, Issue 2 https://doi.org/10.1063/1.1674033	journal	July 1970
On the absolute thermodynamics of water from computer simulations: A comparison of first-principles molecular dynamics, reactive and empirical force fields Pascal, Tod A.; Schärf, Daniel; Jung, Yousung The Journal of Chemical Physics, Vol. 137, Issue 24 https://doi.org/10.1063/1.4771974	journal	December 2012
Kemp elimination catalysts by computational enzyme design Röthlisberger, Daniela; Khersonsky, Olga; Wollacott, Andrew M. Nature, Vol. 453, Issue 7192, p. 190-195 https://doi.org/10.1038/nature06879	journal	March 2008
Comparative Protein Structure Modeling Using MODELLER Webb, Benjamin; Sali, Andrej Current Protocols in Bioinformatics, Vol. 47, Issue 1 https://doi.org/10.1002/0471250953.bi0506s47	journal	September 2014
Comparative Protein Structure Modeling Using MODELLER Webb, Benjamin; Sali, Andrej Current Protocols in Bioinformatics, Vol. 54, Issue 1 https://doi.org/10.1002/cpbi.3	journal	June 2016
OpenMM 4: A Reusable, Extensible, Hardware Independent Library for High Performance Molecular Simulation Eastman, Peter; Friedrichs, Mark S.; Chodera, John D. Journal of Chemical Theory and Computation, Vol. 9, Issue 1 https://doi.org/10.1021/ct300857j	journal	November 2012
Polarizable Atomic Multipole Water Model for Molecular Mechanics Simulation Ren, Pengyu; Ponder, Jay W. The Journal of Physical Chemistry B, Vol. 107, Issue 24 https://doi.org/10.1021/jp027815+	journal	May 2003
Polarizable Atomic Multipole-Based Molecular Mechanics for Organic Molecules Ren, Pengyu; Wu, Chuanjie; Ponder, Jay W. Journal of Chemical Theory and Computation, Vol. 7, Issue 10 https://doi.org/10.1021/ct200304d	journal	August 2011
Is the first hydration shell of lysozyme of higher density than bulk water? Merzel, F.; Smith, J. C. Proceedings of the National Academy of Sciences, Vol. 99, Issue 8 https://doi.org/10.1073/pnas.082335099	journal	April 2002
Characterization of the Local Structure in Liquid Water by Various Order Parameters Duboué-Dijon, Elise; Laage, Damien The Journal of Physical Chemistry B, Vol. 119, Issue 26 https://doi.org/10.1021/acs.jpcb.5b02936	journal	June 2015
Protein hydration dynamics in aqueous solution Denisov, Vladimir P.; Halle, Bertil Faraday Discussions, Vol. 103 https://doi.org/10.1039/fd9960300227	journal	January 1996
Description of Hydration Water in Protein (Green Fluorescent Protein) Solution Perticaroli, Stefania; Ehlers, Georg; Stanley, Christopher B. Journal of the American Chemical Society, Vol. 139, Issue 3 https://doi.org/10.1021/jacs.6b08845	journal	November 2016
Biological water at the protein surface: Dynamical solvation probed directly with femtosecond resolution Pal, S. K.; Peon, J.; Zewail, A. H. Proceedings of the National Academy of Sciences, Vol. 99, Issue 4 https://doi.org/10.1073/pnas.042697899	journal	February 2002
Dynamics in Protein Powders on the Nanosecond–Picosecond Time Scale Are Dominated by Localized Motions Nickels, Jonathan D.; García Sakai, Victoria; Sokolov, Alexei P. The Journal of Physical Chemistry B, Vol. 117, Issue 39 https://doi.org/10.1021/jp4058884	journal	September 2013
Molecular properties of aqueous solutions: a focus on the collective dynamics of hydration water Comez, L.; Paolantoni, M.; Sassi, P. Soft Matter, Vol. 12, Issue 25 https://doi.org/10.1039/C5SM03119B	journal	January 2016
A universal scaling law for atomic diffusion in condensed matter Dzugutov, Mikhail Nature, Vol. 381, Issue 6578 https://doi.org/10.1038/381137a0	journal	May 1996
Site-resolved measurement of water-protein interactions by solution NMR Nucci, Nathaniel V.; Pometun, Maxim S.; Wand, A. Joshua Nature Structural & Molecular Biology, Vol. 18, Issue 2 https://doi.org/10.1038/nsmb.1955	journal	January 2011
Exploring challenges in rational enzyme design by simulating the catalysis in artificial kemp eliminase Frushicheva, M. P.; Cao, J.; Chu, Z. T. Proceedings of the National Academy of Sciences, Vol. 107, Issue 39 https://doi.org/10.1073/pnas.1010381107	journal	September 2010
Challenges and Advances in Validating Enzyme Design Proposals: The Case of Kemp Eliminase Catalysis Frushicheva, Maria P.; Cao, Jie; Warshel, Arieh Biochemistry, Vol. 50, Issue 18 https://doi.org/10.1021/bi200063a	journal	May 2011

Cited By (3)

Perspective: Computational chemistry software and its advancement as illustrated through three grand challenge cases for molecular science Krylov, Anna; Windus, Theresa L.; Barnes, Taylor The Journal of Chemical Physics, Vol. 149, Issue 18 https://doi.org/10.1063/1.5052551	journal	November 2018
Calculating free energies from the vibrational density of states function: Validation and critical assessment Peters, Laurens D. M.; Dietschreit, Johannes C. B.; Kussmann, Jörg The Journal of Chemical Physics, Vol. 150, Issue 19 https://doi.org/10.1063/1.5079643	journal	May 2019
Disassembling solvation free energies into local contributions—Toward a microscopic understanding of solvation processes Heyden, Matthias WIREs Computational Molecular Science, Vol. 9, Issue 2 https://doi.org/10.1002/wcms.1390	journal	July 2018

Figures / Tables (6)

Similar Records

The Importance of the Scaffold for de Novo Enzymes: A Case Study with Kemp Eliminase

Journal Article · Thu Apr 06 00:00:00 EDT 2017 · Journal of the American Chemical Society · OSTI ID:1532319

Bhowmick, Asmit; Sharma, Sudhir C.; Head-Gordon, Teresa

The role of side chain entropy and mutual information for improving the de novo design of Kemp eliminases KE07 and KE70

Journal Article · Fri Jun 24 00:00:00 EDT 2016 · Physical Chemistry Chemical Physics. PCCP · OSTI ID:1532319

Bhowmick, Asmit; Sharma, Sudhir C.; Honma, Hallie; +1 more

Computational Optimization of Electric Fields for Improving Catalysis of a Designed Kemp Eliminase

Journal Article · Tue Nov 21 00:00:00 EST 2017 · ACS Catalysis · OSTI ID:1532319

Vaissier, Valerie; Sharma, Sudhir C.; Schaettle, Karl; +2 more

Related Subjects

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY