Multiscale Simulations Reveal Distal Allosteric Reprogramming of Pocket Dynamics and Dual Hydrolytic Pathways in Engineered Methyl Parathion Hydrolase
-bound water molecule or a bridging hydroxide. In parallel, long-range allosteric communication modulates enzyme flexibility in a temperature-dependent manner, thereby tuning thermostability. Distinct mechanistic modes are suggested: MPHase-m5a enhances thermostability through local rigidification, whereas MPHase-m5b preserves productive dynamics to achieve higher catalytic efficiency. These findings highlight distal allostery as a useful design principle for simultaneously optimizing catalytic activity and thermostability in detoxifying hydrolases.
Authors
- Yubing Si (ORCID: https://orcid.org/0000-0003-3593-5941)
- Zexing Cao (ORCID: https://orcid.org/0000-0003-0803-7732)
- Yuan Zhao (ORCID: https://orcid.org/0000-0001-6586-4350)
- Yuzhuang Fu (ORCID: https://orcid.org/0009-0009-1987-0341)
- Xiaoyuan Liu (ORCID: https://orcid.org/0000-0001-9259-7016)
- Zhiyang Zhang (ORCID: https://orcid.org/0000-0002-2930-5575)
- Nan Lv (ORCID: https://orcid.org/0000-0002-6985-2581)
- Jun Yu
Institutions
- China Pharmaceutical University (CN)
- Henan University (CN)
- Xiamen University (CN)
- Huzhou Normal University (CN)
- Zhengzhou University (CN)
- First Affiliated Hospital of Henan University of Traditional Chinese Medicine (CN)
- Health & Life (Taiwan) (TW)
- Henan Normal University (CN)
Publication Details
- Journal
- The Journal of Physical Chemistry B
- Published
- 2026-04-27
- DOI
- https://doi.org/10.1021/acs.jpcb.6c01732
- Primary Topic
- Biochemical Acid Research Studies
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Natural Science Foundation of China
- Natural Science Foundation of Henan Province