期刊
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
卷 19, 期 24, 页码 15709-15714出版社
ROYAL SOC CHEMISTRY
DOI: 10.1039/c7cp02198d
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资金
- IBM Bluegene Science Program [W125859, W1464125, W1464164]
Candida antarctica lipase B (CalB), resembling many other lipases structure-wise, contains a flexible lid that undergoes a surprisingly large conformational change when catalyzing hydrophobic substrates (e.g. triglycerides). Despite extensive and important applications in industry, it is so far still elusive whether CalB can be activated on a hydrophobic surface, like other lipases. From large-scale all-atom molecular dynamics simulations, we discovered an open state that strikingly shows a much wider and more stable entrance to the catalytic site than the one suggested by previous crystal structures. Simulations demonstrate that in the newly found open state CalB possesses a lid-holder'' structure that intimately harbors the lid of CalB, i.e. a remarkable self-activation mechanism. To account for the unusual interfacial activation of CALB revealed in a recent experiment, we further introduce a simple model: the activation occurs only when the binding free energy between the lid and a hydrophobic surface is larger than a critical value, 4.0 kcal mol(-1) that is the one between the lid and the lid-holder''. Our findings shed light on possible protein engineering of lipases to permit either self-activation with broadened catalytic targets (including water soluble ones) or surface activation with elevated activities.
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