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

Belsare, S., Pattni, V., Heyden, M., & Head-Gordon, T. (2018). Solvent Entropy Contributions to Catalytic Activity in Designed and Optimized Kemp Eliminases. The Journal of Physical Chemistry B, 122(21), 5300-5307. doi:10.1021/acs.jpcb.7b07526.

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jp7b07526_si_001.pdf (Supplementary material), 497KB
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 Creators:
Belsare, Saurabh1, Author
Pattni, Viren2, Author           
Heyden, Matthias2, Author           
Head-Gordon, Teresa1, 3, 4, 5, 6, 7, Author
Affiliations:
1The UC Berkeley-UCSF Graduate Program in Bioengineering, ou_persistent22              
2Research Group Heyden, Max-Planck-Institut für Kohlenforschung, Max Planck Society, ou_1950292              
3Kenneth S. Pitzer Center for Theoretical Chemistry, ou_persistent22              
4Department of Chemistry, ou_persistent22              
5Department of Bioengineering, ou_persistent22              
6Department of Chemical and Biomolecular Engineering, University of California, ou_persistent22              
7Chemical Sciences Division, Lawrence Berkeley National Labs, Berkeley, CA, 94720, ou_persistent22              

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 Abstract: We analyze 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 indicates 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.

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Language(s): eng - English
 Dates: 2017-09-052017-07-292017-09-052017-09-122018-05-31
 Publication Status: Published in print
 Pages: 8
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1021/acs.jpcb.7b07526
 Degree: -

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Title: The Journal of Physical Chemistry B
  Other : J. Phys. Chem. B
Source Genre: Journal
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Publ. Info: Washington, D.C. : American Chemical Society
Pages: - Volume / Issue: 122 (21) Sequence Number: - Start / End Page: 5300 - 5307 Identifier: ISSN: 1520-6106
CoNE: https://pure.mpg.de/cone/journals/resource/1000000000293370_1