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Aldol additions with mutant lipase: analysis by experiments and theoretical calculations

2004; Elsevier BV; Volume: 31; Issue: 4-6 Linguagem: Inglês

10.1016/j.molcatb.2004.08.005

1873-3158

Cecilia Branneby, Peter Carlqvist, Karl Hult, Tore Brinck, Per Berglund,

Cyclopropane Reaction Mechanisms

A Ser105Ala mutant of Candida antarctica lipase B has previously been shown to catalyze aldol additions. Quantum chemical calculations predicted a reaction rate similar to that of natural enzymes, whereas experiments showed a much lower reaction rate. Molecular dynamics simulations, presented here, show that the low reaction rate is a consequence of the low frequencies of near attack complexes in the enzyme. Equilibrium was also considered as a reason for the slow product formation, but could be excluded by performing a sequential reaction to push the reaction towards product formation. In this paper, further experimental results are also presented, highlighting the importance of the entire active site for catalysis.