STRUCTURAL INVESTIGATIONS OF THE REGIOSELECTIVITY AND ENANTIOSELECTIVITY OF LIPASES

Although lipases are widely applied for the stereospecific resolution of racemic mixtures of esters, the atomic details of the factors that are responsible for their stereospecificity are largely obscure. We de termined the X-ray structures of Pseudomonas cepacia lipase in complex with two enantiopure triglyceride analogues, that closely mimic natur al substrates. This allowed an unambiguous view of how the two wings o f the boomerang-shaped active site accommodate the acyl and alcohol pa rts of the triglyceride. The binding groove for the hydrophobic sn-3 f atty acid chain is large and hydrophobic. The cleft for the alcohol mo iety is divided in two parts, one tightly binding the sn-2 acyl chain with hydrophilic and hydrophobic interactions, the other more weakly b inding the sn-l fatty acid. The enantioselectivity of Pseudomonas cepa cia lipase seems therefore to be predominantly determined by the size and interactions of the sn-2 chain and by the size of the sn-3 chain. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.