Computational study of the enantioselectivity of the O-acetylation of (R,S)-propranolol catalyzed by Candida antarctica lipase B
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2014-10
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Abstract
Candida antarctica lipase B (CalB) displaysmoderate enantioselectivity when it catalyzes the acetylation of
(R,S)-propranolol, favoring the faster transformation of the R-propranolol. With the aim to better understand the enantioselectivity of this reaction, we have performed a molecular dynamics (MD) study of the
enzyme substrate complexes. Reactive enzyme substrate complexes were identified for both enantiomers
of propranolol, which differ in their temporal stability and in their ability to reach the corresponding
transition states (TS). Reactive complexes of R-propranolol present a better ability to be transformed
by CalB than those of S-propranolol. This allows us to explain the enantioselectivity. Analysis of the
enzyme–substrate interactions suggests thatthe CH- interactions betweenthenaphthyl rings of propranolol and the residues of the CalB binding pocket may play an important role in stabilizing the transition
states involved in the transformation of the R-propranolol. The residues Ile189, Ala282 and Leu278 were
identified as key residues for the enantioselectivity of CalB.
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