Journal Article

FZJ-2021-02622

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Promiscuous Esterases Counterintuitively Are Less Flexible than Specific Ones

Nutschel, C.FZJ* ; Coscolín, C. ; David, B. ; Mulnaes, D. ; Ferrer, M. ; Jaeger, K.-E.FZJ* ; Gohlke, H. (Corresponding author)FZJ*

2021
American Chemical Society Washington, DC

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Please use a persistent id in citations: http://hdl.handle.net/2128/27975  doi:10.1021/acs.jcim.1c00152

Abstract: 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.

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Contributing Institute(s):

1. Bioinformatik (IBG-4)
2. John von Neumann - Institut für Computing (NIC)
3. Jülich Supercomputing Center (JSC)
4. Strukturbiochemie (IBI-7)

Research Program(s):

1. 5111 - Domain-Specific Simulation & Data Life Cycle Labs (SDLs) and Research Groups (POF4-511) (POF4-511)
2. 2171 - Biological and environmental resources for sustainable use (POF4-217) (POF4-217)
3. 2172 - Utilization of renewable carbon and energy sources and engineering of ecosystem functions (POF4-217) (POF4-217)
4. 511 - Computational Science and Mathematical Methods (POF3-511) (POF3-511)
5. Forschergruppe Gohlke (hkf7_20200501) (hkf7_20200501)

Appears in the scientific report 2021

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Database coverage:
; ; Clarivate Analytics Master Journal List ; Current Contents - Physical, Chemical and Earth Sciences ; Essential Science Indicators ; IF < 5 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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