Substrate entropy in enzyme enantioselectivity : An experimental and molecular modeling study of a lipase

• The temperature dependence of the enantioselectivity of Candida antarctica lipase B for 3-hexanol, 2-butanol, 3-methyl-2-butanol, 3,3-dimethyl-2-butanol, and 1-bromo-2-butanol revealed that the differential activation entropy, Delta(R-S)Delta(S)(divided bydivided by)., was as significant as the differential activation enthalpy, Delta(R-S)DeltaH(divided bydivided by), to the enantiomeric ratio, E. 1-Bromo-2-butanol, with isosteric substituents, displayed the largest Delta(R-S)DeltaS(divided bydivided by) 3-Hexanol displayed, contrary to other sec-alcohols, a positive Delta(R-S)DeltaS(divided bydivided by). In other words, for 3-hexanol the preferred R-enantiomer is not only favored by enthalpy but also by entropy. Molecular dynamics (MID) simulations and systematic search calculations of the substrate accessible volume within the active site revealed that the (R)-3-hexanol transition state (TS) accessed a larger volume within the active site than the (S)-3-hexanol TS. This correlates well with the hi-her TS entropy of (R)-3-hexanol. In addition, this enantiomer did also yield a higher number of allowed conformations, N, from the systematic search routines, than did the S-enantiomer. The substrate accessible volume was greater for the enantiomer preferred by entropy also for 2-butanol. For 3,3-dimethyl-2-butanol, however, neither MD-simulations nor systematic search calculations yielded substrate accessible volumes that correlate to TS entropy. Ambiguous results were achieved for 3-methyl-2-butanol.

Ämnesord

TEKNIK OCH TEKNOLOGIER  -- Industriell bioteknik (hsv//swe)

ENGINEERING AND TECHNOLOGY  -- Industrial Biotechnology (hsv//eng)

Nyckelord

molecular dynamics; systematic search; enthalpy; enantiomeric ratio; Candida antarctica

Bioengineering

Bioteknik

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