Activation and friction in enzymatic loop opening and closing dynamics
![Thumbnail](/xmlui/bitstream/handle/10234/207494/89711_RamosGuzmanCA_2024.pdf.jpg?sequence=5&isAllowed=y)
View/ Open
Impact
![Google Scholar](/xmlui/themes/Mirage2/images/uji/logo_google.png)
![Microsoft Academico](/xmlui/themes/Mirage2/images/uji/logo_microsoft.png)
Metadata
Show full item recordcomunitat-uji-handle:10234/9
comunitat-uji-handle2:10234/160292
comunitat-uji-handle3:10234/160293
comunitat-uji-handle4:
INVESTIGACIONMetadata
Title
Activation and friction in enzymatic loop opening and closing dynamicsAuthor (s)
Date
2024-03-20Publisher
Springer NatureISSN
2041-1723Bibliographic citation
Zinovjev, K., Guénon, P., Ramos-Guzmán, C.A. et al. (2024). Activation and friction in enzymatic loop opening and closing dynamics. Nature Communications 15, 2490.Type
info:eu-repo/semantics/articleVersion
info:eu-repo/semantics/publishedVersionSubject
Abstract
Protein loop dynamics have recently been recognized as central to enzymatic activity, specificity and stability. However, the factors controlling loop opening and closing kinetics have remained elusive. Here, we combine ... [+]
Protein loop dynamics have recently been recognized as central to enzymatic activity, specificity and stability. However, the factors controlling loop opening and closing kinetics have remained elusive. Here, we combine molecular dynamics simulations with string-method determination of complex reaction coordinates to elucidate the molecular mechanism and rate-limiting step for WPD-loop dynamics in the PTP1B enzyme. While protein conformational dynamics is often represented as diffusive motion hindered by solvent viscosity and internal friction, we demonstrate that loop opening and closing is activated. It is governed by torsional rearrangement around a single loop peptide group and by significant friction caused by backbone adjustments, which can dynamically trap the loop. Considering both torsional barrier and time-dependent friction, our calculated rate constants exhibit very good agreement with experimental measurements, reproducing the change in loop opening kinetics between proteins. Furthermore, we demonstrate the applicability of our results to other enzymatic loops, including the M20 DHFR loop, thereby offering prospects for loop engineering potentially leading to enhanced designs. [-]
Is part of
Nature Communications, Vol. 15 (2024)Funder Name
Ministerio de Ciencia e Innovación / Agencia Estatal de Investigación | Generalitat Valenciana
Project code
PID2021-123332OB-C22 | PROMETEO CIPROM/2021/079
Rights
info:eu-repo/semantics/openAccess
This item appears in the folowing collection(s)
- INAM_Articles [521]