Functional Motions of Candida antarctica Lipase B: A Survey through Open-Close Conformations

Abstract

Candida antarctica lipase B (CALB) belongs to psychrophilic lipases which hydrolyze carboxyl ester bonds at low temperatures. There have been some features reported about cold-activity of the enzyme through experimental methods, whereas there is no detailed information on its mechanism of action at molecular level. Herein, a comparative molecular dynamics simulation and essential dynamics analysis have been carried out at three temperatures (5, 35 and 50°C) to trace the dominant factors in the psychrophilic properties of CALB under cold condition. The results clearly describe the effect of temperature on CALB with meaningful differences in the flexibility of the lid region (α5 helix), covering residues 141–147. Open- closed conformations have been obtained from different sets of long-term simulations (60 ns) at 5°C gave two reproducible distinct forms of CALB. The starting open conformation became closed immediately at 35 and 50°C during 60 ns of simulation, while a sequential open-closed form was observed at 5°C. These structural alterations were resulted from α5 helical movements, where the closed conformation of active site cleft was formed by displacement of both helix and its side chains. Analysis of normal mode showed concerted motions that are involved in the movement of both α5 and α10 helices. It is suggested that the functional motions needed for lypolytic activity of CALB is constructed from short-range movement of α5, accompanied by long-range movement of the domains connected to the lid region.

Controlled fragrance delivery in functionalised ionic liquid-enzyme systems

“…5 mM. This relatively small change in the menthol release during the micellisation is in agreement with the fact that highly stereospecific lipase B from Candida Antarctica does not have a prominent interfacial activation on supersubstrates, 29 although some changes of the lid structure of the enzyme take place 30 at the water-oil interface that can affect its catalytic activity. In contrast, [C 4 menim]Cl shows no break point.…”

Lipase adsorption on different nanomaterials: a multi-scale simulation study

“…The highly dynamic character exhibited by helix a 5 and helix a 10 was also demonstrated by previous results. 38,39 Residues 138-152 have the largest RMSF values of greater than 2 Å on COOH-SAM, followed by the intermediate behaviors on rutile and NH 2 -SAM surfaces; these residues show the smallest variation on the graphite surface. The N-terminal region of lipase on graphite exhibits a higher flexibility than those in a bulk solution milieu and on other three surfaces.…”

“…In aqueous media, the lid switches from an open conformation to a closed one while the reverse motion occurs in an organic environment. Ranjbar et al 38 employed MD and nuclear magnetic resonance to probe the local flexibility and large-scale motions of CalB and also the open-closed conformations of the lid at different temperatures. The activation mechanism of Yarrowia lipolytica lipase immobilised on carbon nanotubes was investigated to elucidate the lid opening mechanism derived from the interactions between lipase and the hydrophobic surface.…”

Engineering Lipases: walking the fine line between activity and stability

“…However, the presence of the lid domain is debated. [99][100][101] Interfacial activation, which is considered the signature for lid mechanism, is reported to substrates such as secondary alcohol with one substituent being an ethyl group. 102,103 Based on the idea of the narrow opening to the active site, Magnusson et al 104 used site-directed mutagenesis to engineer CALB for larger substrates.…”