Polarity Triggers Interfacial Opening in Lid-Architecture Lipases: A Comparative Study of Pseudomonas cepacia Lipase and Candida antarctica Lipase B.

2026-04-09
Langmuir : the ACS journal of surfaces and colloids 42(15)

PubMed: 41955104
DOI: 10.1021/acs.langmuir.6c00507

Study Design

Methods: Experimental assays and molecular dynamics simulations

Microbial lipases are versatile biocatalysts that are essential for hydrolyzing ester bonds in triglycerides. Among these enzymes, Pseudomonas cepacia lipase (PCL) possesses a canonical lid domain, whereas Candida antarctica lipase B (CALB) features a rigid lid-like structure. Understanding how these different structures catalyze mechanisms differently at the interface is crucial. Experimental assays demonstrated high activity for both enzymes in aqueous systems, but CALB exhibited lower activity than PCL in biphasic water-organic solvent systems. Molecular dynamics simulations were employed to investigate the conformational dynamics and interfacial interactions. The results reveal that the PCL undergoes polarity-induced conformational changes leading to channel shortening and bottleneck widening, thereby facilitating substrate access. In contrast, CALB retains a rigid architecture with fixed distances between the lid-like region and the catalytic triad, thereby limiting interfacial adaptability. PCL further employs a lid-mediated adsorption mechanism that enhances interfacial binding and exposes hydrophobic residues. Conversely, CALB relies on an active-site-oriented approach with a weaker interfacial affinity. Additionally, the aqueous environment promotes lid closure in lipase PCL by stabilizing hydrogen bond networks and inducing conformational shifts in key flexible regions. This study elucidates polarity-driven interfacial activation mechanisms distinguishing lid-containing and lid-like lipases, offering atomistic insights for rational lipase engineering in nonaqueous environments.

Research Insights

Supplement	Dose	Health Outcome	Effect Type	Effect Size	Source