Stereoselective catalysis controlled by a native leucine or variant isoleucine wing‐gatekeeper in 2‐haloacid dehalogenase. Issue 3 (28th December 2018)

• Record Type: Journal Article
• Authors: Feng, Yanbin; Wang, Yayue; Chu, Huiying; Fan, Yan; Cao, Xupeng; Liu, Yinghui; Li, Guohui; Xue, Song
• Is Part Of: FEBS letters. Volume 593:Issue 3(2019)
• Page Start: 308
• Page End: 318
• Publication Date: 2018-12-28
• Subjects: biocatalyst -- enzyme -- molecular dynamics -- protein engineering -- stereoselectivity; Biochemistry -- Periodicals; Biophysics -- Periodicals; Molecular biology -- Periodicals; Biochimie -- Périodiques; Biochemistry; Biophysics; Molecular biology; Periodicals; 572.05
• DOI: 10.1002/1873-3468.13309
• Languages: English
• ISSNs: 0014-5793

Abstract

Abstract : Comprehensively understanding enzymatic stereoselectivity will assist in the creation of new enzymes for producing optically pure compounds for chemical applications. The essential features for selecting enantiomers are controlled by particular residues or regions of the enzymes. We report a stereoselective mechanism in the D‐2‐haloacid dehalogenase HadD AJ1, in which L288 is identified as a gatekeeper in the access channel that strictly recognizes D‐enantiomers. Mutagenesis of L288 to isoleucine (I) enlarges the size of the channel and allows the enzyme to accommodate L‐enantiomers. Furthermore, the wing flip of I288 induces hydrophobic interactions with the L‐enantiomer and directly affects the catalytic efficiency. The results illustrate the dynamic catalytic mechanisms of Leu‐Ile gatekeepers and provide knowledge for unveiling the basis of stereospecificity in biocatalysts.