Browsing by Author "Wang, Tsai-Ting"

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Alteration of the Substrate's Prefolded Conformation and Cyclization Stereochemistry of Oxidosqualene-Lanosterol Cyclase of Saccharomyces cerevisiae by Substitution at Phenylalanine 699
(2010-02-05)
Wu, Tung-Kung
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Chang, Cheng-Hsiang
;
Wen, Hao-Yu
;
Liu, Yuan-Ting
;
Li, Wen-Hsuan
The Saccharomyces cerevisiae ERG7(Phe699) mutants produced one chair-chair-chair (C-C-C) and two chair-boat-chair (C-B-C) truncated tricyclic compounds, one tetracyclic 17 alpha-exocyclic unrearranged intermediate, and two 17 beta-exocyclic truncated rearranged intermediates. These results provided direct evidence for the importance of the residue in affecting mechanistic transitions between C-B-C and C-C-C substrate conformation and between the 17 alpha- and 17 beta-exocyclic side chain stereochemistry as well as in stabilizing the 6 -6-5 tricyclic and the protosteryl C-17 cations.
Importance of Saccharomyces cerevisiae Oxidosqualene-Lanosterol Cyclase Tyrosine 707 Residue for Chair-Boat Bicyclic Ring Formation and Deprotonation Reactions
(2008-11-06)
Wu, Tung-Kung
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Wang, Tsai-Ting
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Chang, Cheng-Hsiang
;
Liu, Yuan-Ting
;
Shie, Wen-Shiang
A contact mapping strategy was applied to identity putative amino acid residues that influence the oxidosqualene-lanosterol B-ring cyclization reaction. A bicyclic intermediate with two altered deprotonation products, in conjunction with lanosterol, were isolated from the ERG7(Y707X) mutants, indicating that the Tyr707 residue may play a functional role in stabilizing the chair-boat bicyclic C-8 cation and the lanosteryl C-8/C-9 cation intermediates.
Saccharomyces cerevisiae Oxidosqualene-Lanosterol Cyclase: A Chemistry-Biology Interdisciplinary Study of the Protein's Structure-Function-Reaction Mechanism Relationships
(2008)
Wu, Tung-Kung
;
Chang, Cheng-Hsiang
;
Liu, Yuan-Ting
;
Wang, Tsai-Ting
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生物科技學系
The oxidosqualene cyclases (EC 5.4.99-) constitute a family of enzymes that catalyze diverse cyclization/rearrangement reactions of (3S)-2,3-oxidosqualene into a distinct array of sterols and triterpenes. The relationship between the cyclization mechanism and the enzymatic structure is extremely complex and compelling. This review covers the historical achievements of biomimetic studies and current progress in structural biology, molecular genetics, and bioinformatics studies to elucidate the mechanistic and structure-function relationships of the Saccharomyces cerevisiae oxidosqualene-lanosterol cyclase-catalyzed cyclization/rearrangement reaction. (C) 2008 The Japan Chemical journal Forum and Wiley Periodicals, Inc. Chem Rec 8: 302-325; 2008: Published online in Wiley, InterScience (www.interscience.wiley.com) DOI 10. 1002/tcr.20157
The cysteine 703 to isoleucine or histidine mutation of the oxidosqualene-lanosterol cyclase from Saccharomyces cerevisiae generates an iridal-type triterpenoid
(2012-11-01)
Chang, Cheng-Hsiang
;
Chen, Yi-Chi
;
Tseng, Sheng-Wei
;
Liu, Yuan-Ting
;
Wen, Hao-Yu
The Cys703 to Ile or His mutation within Saccharomyces cerevisiae oxidosqualene-lanosterol cyclase ERG7 (ERG7(C7031/H)) generates an unusual truncated bicyclic rearranged intermediate, (8R,9R,10R)-polypoda-5,13E,17E,21-tetraen-3 beta-ol, related to iridal-skeleton triterpenoid. Numerous oxidosqualene-cyclized truncated intermediates, including tricyclic, unrearranged tetracyclic with 17 alpha/beta exocyclic hydrocarbon side chain, rearranged tetracyclic, and chair chair chair tricyclic intermediates (compounds 3-9), were also isolated from the ERG7(C703X) site-saturated mutations or the ERG7(F699T/C7031) double mutation, indicating the functional role of the Cys703 residue in stabilizing the bicyclic C-8 cation and the rearranged intermediate or interacting with Phe699, and opened a new avenue of engineering ERG7 for producing biological active agents. (C) 2012 Elsevier Masson SAS. All rights reserved.