Self-Assembly Nanostructures of Triglyceride–Water Interfaces Determine Functional Conformations of Candida antarctica Lipase B

Candida antarctica lipase B (CalB) acts as a lipase when adsorbed to an acylglyceride interface and as an esterase when exposed to an aqueous environment. The effect of the molecular self-assembly nanostructure of triglyceride-water interfaces on structural conformations of adsorbed CalB and the implications to its catalytic function were studied by molecular dynamics simulations. Systems of CalB adsorbed to interfaces and solvated in water were compared. The two environments induced relative motions of helices α5 and α10 that resulted in open and closed conformations. The open conformation was stabilized by interactions between the polar and nonpolar amino acids of α5 and α10 and the nanostructure of triglyceride aggregates, which self-assembled into crystalline-like patterns of alternating polar and nonpolar lamellae. Thus, the structure of CalB has been adapted by evolution to the geometric constraints imposed by the interface nanostructure for optimized catalytic activity. Helices α5 and α10 have two functions. As mobile elements, they ensure access of bulky substrates to the active site in the open conformation. As a part of the active site pocket, they ensure binding of substrate molecules in a productive orientation near the active site. In water, access to the binding site is limited, and the smaller substrate binding site is beneficial for the binding of small, water-soluble substrates. The CalB crystal structure commonly used for protein engineering studies represents an intermediate state between open and closed, and may thus not be adequate to assess the function of CalB, neither as lipase nor as esterase.