TY  - JOUR
AU  - Nutschel, Christina
AU  - Coscolín, Cristina
AU  - David, Benoit
AU  - Mulnaes, Daniel
AU  - Ferrer, Manuel
AU  - Jaeger, Karl-Erich
AU  - Gohlke, Holger
TI  - Promiscuous Esterases Counterintuitively Are Less Flexible than Specific Ones
JO  - Journal of chemical information and modeling
VL  - 61
IS  - 5
SN  - 1549-960X
CY  - Washington, DC
PB  - American Chemical Society
M1  - FZJ-2021-02622
SP  - 2383 - 2395
PY  - 2021
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - 33949194
UR  - <Go to ISI:>//WOS:000656118800025
DO  - DOI:10.1021/acs.jcim.1c00152
UR  - https://juser.fz-juelich.de/record/893205
ER  -