Crystal structures of ligand-bound octaprenyl pyrophosphate synthase from Escherichia coli reveal the catalytic and chain-length determining mechanisms

Xu Han; Chun Chi Chen; Chih Jung Kuo; Chun Hsiang Huang; Yingying Zheng; Tzu Ping Ko; Zhen Zhu; Xinxin Feng; Ke Wang; Eric Oldfield; Andrew H.J. Wang; Po Huang Liang; Rey Ting Guo; Yanhe Ma

doi:10.1002/prot.24618

Crystal structures of ligand-bound octaprenyl pyrophosphate synthase from Escherichia coli reveal the catalytic and chain-length determining mechanisms

Xu Han, Chun Chi Chen, Chih Jung Kuo, Chun Hsiang Huang, Yingying Zheng, Tzu Ping Ko, Zhen Zhu, Xinxin Feng, Ke Wang, Eric Oldfield, Andrew H.J. Wang, Po Huang Liang, Rey Ting Guo, Yanhe Ma

Chemistry

Research output: Contribution to journal › Article › peer-review

Abstract

Octaprenyl pyrophosphate synthase (OPPs) catalyzes consecutive condensation reactions of one allylic substrate farnesyl pyrophosphate (FPP) and five homoallylic substrate isopentenyl pyrophosphate (IPP) molecules to form a C₄₀ long-chain product OPP, which serves as a side chain of ubiquinone and menaquinone. OPPs belongs to the trans-prenyltransferase class of proteins. The structures of OPPs from Escherichia coli were solved in the apo-form as well as in complexes with IPP and a FPP thio-analog, FsPP, at resolutions of 2.2-2.6 Å, and revealed the detailed interactions between the ligands and enzyme. At the bottom of the active-site tunnel, M123 and M135 act in concert to form a wall which determines the final chain length. These results represent the first ligand-bound crystal structures of a long-chain trans-prenyltransferase and provide new information on the mechanisms of catalysis and product chain elongation.

Original language	English (US)
Pages (from-to)	37-45
Number of pages	9
Journal	Proteins: Structure, Function and Bioinformatics
Volume	83
Issue number	1
DOIs	https://doi.org/10.1002/prot.24618
State	Published - Jan 2015

Keywords

Crystal structure
Prenyltransferase
Product chain length
Site-directed mutagenesis

ASJC Scopus subject areas

Structural Biology
Biochemistry
Molecular Biology

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10.1002/prot.24618

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Han, X., Chen, C. C., Kuo, C. J., Huang, C. H., Zheng, Y., Ko, T. P., Zhu, Z., Feng, X., Wang, K., Oldfield, E., Wang, A. H. J., Liang, P. H., Guo, R. T., & Ma, Y. (2015). Crystal structures of ligand-bound octaprenyl pyrophosphate synthase from Escherichia coli reveal the catalytic and chain-length determining mechanisms. Proteins: Structure, Function and Bioinformatics, 83(1), 37-45. https://doi.org/10.1002/prot.24618

Han, X, Chen, CC, Kuo, CJ, Huang, CH, Zheng, Y, Ko, TP, Zhu, Z, Feng, X, Wang, K, Oldfield, E, Wang, AHJ, Liang, PH, Guo, RT & Ma, Y 2015, 'Crystal structures of ligand-bound octaprenyl pyrophosphate synthase from Escherichia coli reveal the catalytic and chain-length determining mechanisms', Proteins: Structure, Function and Bioinformatics, vol. 83, no. 1, pp. 37-45. https://doi.org/10.1002/prot.24618

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title = "Crystal structures of ligand-bound octaprenyl pyrophosphate synthase from Escherichia coli reveal the catalytic and chain-length determining mechanisms",

abstract = "Octaprenyl pyrophosphate synthase (OPPs) catalyzes consecutive condensation reactions of one allylic substrate farnesyl pyrophosphate (FPP) and five homoallylic substrate isopentenyl pyrophosphate (IPP) molecules to form a C40 long-chain product OPP, which serves as a side chain of ubiquinone and menaquinone. OPPs belongs to the trans-prenyltransferase class of proteins. The structures of OPPs from Escherichia coli were solved in the apo-form as well as in complexes with IPP and a FPP thio-analog, FsPP, at resolutions of 2.2-2.6 {\AA}, and revealed the detailed interactions between the ligands and enzyme. At the bottom of the active-site tunnel, M123 and M135 act in concert to form a wall which determines the final chain length. These results represent the first ligand-bound crystal structures of a long-chain trans-prenyltransferase and provide new information on the mechanisms of catalysis and product chain elongation.",

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AU - Zheng, Yingying

AU - Ko, Tzu Ping

AU - Zhu, Zhen

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Crystal structures of ligand-bound octaprenyl pyrophosphate synthase from Escherichia coli reveal the catalytic and chain-length determining mechanisms

Abstract

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