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, ΔR−SΔS‡, was as significant as the differential activation enthalpy, ΔR−S...
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Published in | Protein science Vol. 11; no. 6; pp. 1462 - 1471 |
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Main Authors | , , |
Format | Journal Article |
Language | English |
Published |
Bristol
Cold Spring Harbor Laboratory Press
01.06.2002
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Subjects | |
Online Access | Get full text |
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Summary: | 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, ΔR−SΔS‡, was as significant as the differential activation enthalpy, ΔR−SΔH‡, to the enantiomeric ratio, E. 1‐Bromo‐2‐butanol, with isosteric substituents, displayed the largest ΔR−SΔS‡. 3‐Hexanol displayed, contrary to other sec‐alcohols, a positive ΔR−SΔS‡. In other words, for 3‐hexanol the preferred R‐enantiomer is not only favored by enthalpy but also by entropy. Molecular dynamics (MD) 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 higher 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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Reprint requests to: Karl Hult, Department of Biotechnology, Stockholm Center for Physics, Astronomy and Biotechnology, Royal Institute of Technology, SE-106 91 Stockholm, Sweden; e-mail: kalle@biochem.kth.se; fax: 46-8-553-784-68. Article and publication are at http://www.proteinscience.org/cgi/doi/10.1110/ps.3480102. |
ISSN: | 0961-8368 1469-896X 1469-896X |
DOI: | 10.1110/ps.3480102 |