TY - JOUR
T1 - Crystal Structure and Potential Head-to-Middle Condensation Function of a Z,Z-Farnesyl Diphosphate Synthase
AU - Chan, Yueh Te
AU - Ko, Tzu Ping
AU - Yao, Shan Hsueh
AU - Chen, Ya Wen
AU - Lee, Cheng Chung
AU - Wang, Andrew H.J.
N1 - Funding Information:
*E-mail: [email protected]. Tel: +886-2-2785-5696 (C.-C.L.). *E-mail: [email protected]. Tel: +886-2-2788-1981. Fax: +886-2-2788-2043 (A.H.-J.W.). ORCID Yueh-Te Chan: 0000-0002-7759-5511 Funding This work was supported by grants from the Taiwan Protein Project (MOST105-0210-01-12-01 and MOST106-0210-01-15-04), the Academia Sinica-Industrial Technology Research Institute Collaboration Project (23yy-y110505), and Academia Sinica and Ministry of Science and Technology (MOST106-0210-01-15-02). Notes The authors declare no competing financial interest.
Publisher Copyright:
© 2017 American Chemical Society.
PY - 2017/3/31
Y1 - 2017/3/31
N2 - Plants produce a wide variety of secondary metabolites in response to adverse environmental factors. Z,Z-Farnesyl diphosphate (Z,Z-FPP), synthesized by Z,Z-farnesyl diphosphate synthase (zFPS), supports the formation of phytochemicals in wild tomatoes. Here, the crystal structure of N-terminal truncated zFPS (ΔzFPS) was determined. Irregular products including lavandulyl diphosphate and an unknown compound were surprisingly found. Apart from the truncated N-terminus as a functional regulator, structure-based analysis and mutagenesis assays revealed a residue H103 in ΔzFPS as one of the key elements to this irregular function. A series of substrate-enzyme complex structures were obtained from ΔzFPS-H103Y by co-crystallizing with isopentenyl diphosphate, dimethylallyl thiolodiphosphate, or both. Various substrate-binding modes were revealed. The catalytic mechanisms of both the head-to-tail and head-to-middle reactions in ΔzFPS were proposed. Functional switch between the two mechanisms in this enzyme and the essential role played by the flexible C-terminus were elucidated as well.
AB - Plants produce a wide variety of secondary metabolites in response to adverse environmental factors. Z,Z-Farnesyl diphosphate (Z,Z-FPP), synthesized by Z,Z-farnesyl diphosphate synthase (zFPS), supports the formation of phytochemicals in wild tomatoes. Here, the crystal structure of N-terminal truncated zFPS (ΔzFPS) was determined. Irregular products including lavandulyl diphosphate and an unknown compound were surprisingly found. Apart from the truncated N-terminus as a functional regulator, structure-based analysis and mutagenesis assays revealed a residue H103 in ΔzFPS as one of the key elements to this irregular function. A series of substrate-enzyme complex structures were obtained from ΔzFPS-H103Y by co-crystallizing with isopentenyl diphosphate, dimethylallyl thiolodiphosphate, or both. Various substrate-binding modes were revealed. The catalytic mechanisms of both the head-to-tail and head-to-middle reactions in ΔzFPS were proposed. Functional switch between the two mechanisms in this enzyme and the essential role played by the flexible C-terminus were elucidated as well.
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U2 - 10.1021/acsomega.6b00562
DO - 10.1021/acsomega.6b00562
M3 - Article
AN - SCOPUS:85028914166
SN - 2470-1343
VL - 2
SP - 930
EP - 936
JO - ACS Omega
JF - ACS Omega
IS - 3
ER -