Interfacial activation of M37 lipase: A multi-scale simulation study.
Nathalie Willems1, Mickaël Lelimousin1, Heidi Koldsø1
1Department of Biochemistry, University of Oxford, Oxford, United Kingdom.
Biochimica Et Biophysica Acta. Biomembranes
|December 21, 2016
Summary
Psychrophilic lipase M37 activation involves large-scale lid motions at triglyceride interfaces, creating substrate entry pathways. This unique mechanism differs from other lipases, highlighting hydrophobic surface effects on enzyme function.
Area of Science:
- Biochemistry
- Enzymology
- Molecular Biophysics
Background:
- Lipases are crucial enzymes functioning at hydrophobic-aqueous interfaces.
- Hydrophobic interfaces can enhance lipase activity through structural changes, but mechanisms remain unclear.
- Understanding lipase activation is key for biotechnological applications.
Purpose of the Study:
- To investigate how different interfaces affect the conformational dynamics of psychrophilic lipase M37.
- To elucidate the molecular mechanism of lipase M37 activation at hydrophobic interfaces.
- To compare the activation mechanism of M37 with other lipases.
Main Methods:
- Multi-scale molecular dynamics (MD) simulations.
- Simulations of M37 interacting with anionic lipid bilayers and triglyceride surfaces.
- Steered MD simulations for substrate binding analysis.
Main Results:
- M37 lipase interacts with both anionic lipid bilayers and triglyceride surfaces.
- Triglyceride interfaces induce large-scale lid motions (residues 235-283) in M37, opening a substrate entry pathway.
- Hydrophobic residues in lid and active site flap regions (94-110) are exposed during activation.
Conclusions:
- M37 lipase exhibits a distinct activation mechanism at triglyceride interfaces compared to other lipases.
- Interfacial interactions, particularly with triglycerides, are critical for M37 lipase activation.
- The study provides insights into the functional role of hydrophobic surfaces in lipase activation.
