This title appears in the Scientific Report :
2021
Please use the identifier:
http://dx.doi.org/10.1021/acs.jcim.1c00152 in citations.
Please use the identifier: http://hdl.handle.net/2128/27975 in citations.
Promiscuous Esterases Counterintuitively Are Less Flexible than Specific Ones
Promiscuous Esterases Counterintuitively Are Less Flexible than Specific Ones
Understanding mechanisms of promiscuity is increasingly important from a fundamental and application point of view. As to enzyme structural dynamics, more promiscuous enzymes generally have been recognized to also be more flexible. However, examples for the opposite received much less attention. Her...
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Personal Name(s): | Nutschel, Christina |
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Coscolín, Cristina / David, Benoit / Mulnaes, Daniel / Ferrer, Manuel / Jaeger, Karl-Erich / Gohlke, Holger (Corresponding author) | |
Contributing Institute: |
Strukturbiochemie; IBI-7 Jülich Supercomputing Center; JSC John von Neumann - Institut für Computing; NIC Bioinformatik; IBG-4 |
Published in: | Journal of chemical information and modeling, 61 (2021) 5, S. 2383 - 2395 |
Imprint: |
Washington, DC
American Chemical Society
2021
|
DOI: |
10.1021/acs.jcim.1c00152 |
Document Type: |
Journal Article |
Research Program: |
Forschergruppe Gohlke Computational Science and Mathematical Methods Utilization of renewable carbon and energy sources and engineering of ecosystem functions Biological and environmental resources for sustainable use Domain-Specific Simulation & Data Life Cycle Labs (SDLs) and Research Groups |
Link: |
Get full text Published on 2021-05-05. Available in OpenAccess from 2022-05-05. |
Publikationsportal JuSER |
Please use the identifier: http://hdl.handle.net/2128/27975 in citations.
Understanding mechanisms of promiscuity is increasingly important from a fundamental and application point of view. As to enzyme structural dynamics, more promiscuous enzymes generally have been recognized to also be more flexible. However, examples for the opposite received much less attention. Here, we exploit comprehensive experimental information on the substrate promiscuity of 147 esterases tested against 96 esters together with computationally efficient rigidity analyses to understand the molecular origin of the observed promiscuity range. Unexpectedly, our data reveal that promiscuous esterases are significantly less flexible than specific ones, are significantly more thermostable, and have a significantly increased specific activity. These results may be reconciled with a model according to which structural flexibility in the case of specific esterases serves for conformational proofreading. Our results signify that an esterase sequence space can be screened by rigidity analyses for promiscuous esterases as starting points for further exploration in biotechnology and synthetic chemistry. |