INSIGHTS INTO THE MOLECULAR-BASIS FOR FATTY ACYL SPECIFICITIES OF LIPASES FROM GEOTRICHUM-CANDIDUM AND CANDIDA-RUGOSA

Despite immense progress in our comprehension of lipase structure and function during the past decade, the basis for lipase acyl specificiti es has remained poorly understood. This review summarizes some recent advances in the understanding at the molecular-level of substrate acyl recognition by two members in a group of large (M-w similar to 60 kDa ) microbial lipases. Two aspects of acyl specificity will be focused u pon. (1) The unique preference of a fungal Geotrichum candidum lipase for long-chain cis (Delta-9) unsaturated fatty acid moieties in the su bstrate. Mutational analysis of this lipase identified residues essent ial for its anomalous acyl preference. This information highlighted fo r the first time parts in the lipase molecule involved in substrate ac yl differentiation. These results are discussed in the context of the 3D-structure of a G. candidum lipase isoenzyme and structures of the r elated Candida rugosa lipase in complex with inhibitors. (ii) The mech anism by which the yeast C. rugosa lipase discriminates between enanti omers of a substrate with a chiral acyl moiety. Molecular modeling in combination with substrate engineering and kinetic analyses, identifie d two alternative substrate binding modes. This allowed for the propos al of a molecular mechanism explaining how long-chain alcohols can act as enantioselective inhibitors of this enzyme. A picture is thus begi nning to emerge of the interplay between lipase structure and fatty ac yl specificity. (C) 1998 Elsevier Science Ireland Ltd. All rights rese rved.