How Does Lipase Flexibility Affect Its Enantioselectivity in Organic Solvents? A Possible Role of CH⋯π Association in Stabilization of Enzyme-Substrate Complex

Keiichi Watanabe, Tetsuya Uno, Takashi Koshiba, Takashi Okamoto, Yasuhito Ebara, Shin Ichi Ueji

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

For lipase-catalyzed reactions of 2-(4-substitued phenoxy)propionic acids with alcohols in organic solvents containing a small amount of water, the increase of the lipase flexibility brought about by addition of water is found to be favorable for the induced-fit motion of the lipase for the correctly binding enantiomer of the substrate used, thus resulting in the improvement of the lipase enantioselectivity. In particular, for the reaction of the substrate with rich π electron density on its aromatic ring, the enantioselectivity was much more sensitive to the change of the lipase flexibility. Thus, in the induced fit motion, the CH⋯π association between amino acids side chains around the lipase's active site and the aromatic ring of the correctly binding enantiomer is assumed to accelerate the accommodation of the substrate into the lipase's active site and the stabilization of the complex between the enzyme and the substrate. This assumption is also supported by a discussion based on the value of the Michaelis constant obtained. Furthermore, on the basis of a model concerning the acyl-enzyme structure for the incorrectly binding enantiomer, the long alkyl chain alcohols as a nucleophile are found to improve the lipase enantioselectivity markedly.

Original languageEnglish
Pages (from-to)543-548
Number of pages6
JournalBulletin of the Chemical Society of Japan
Volume77
Issue number3
DOIs
Publication statusPublished - 2004
Externally publishedYes

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Enantioselectivity
Lipase
Organic solvents
Stabilization
Substrates
Enzymes
Enantiomers
Alcohols
Nucleophiles
Water
Propionates
Carrier concentration
Association reactions
Amino Acids

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

How Does Lipase Flexibility Affect Its Enantioselectivity in Organic Solvents? A Possible Role of CH⋯π Association in Stabilization of Enzyme-Substrate Complex. / Watanabe, Keiichi; Uno, Tetsuya; Koshiba, Takashi; Okamoto, Takashi; Ebara, Yasuhito; Ueji, Shin Ichi.

In: Bulletin of the Chemical Society of Japan, Vol. 77, No. 3, 2004, p. 543-548.

Research output: Contribution to journalArticle

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