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Title: Structural insights into substrate specificity of Feruloyl-CoA 6’-Hydroxylase from Arabidopsis thaliana

Abstract

Coumarins belong to an important class of plant secondary metabolites. Feruloyl-CoA 6’-hydroxylase (F6’H), a 2-oxoglutarate dependent dioxygenase (2OGD), catalyzes a pivotal step in the biosynthesis of a simple coumarin scopoletin. In this study, we determined the 3-dimensional structure of the F6’H1 apo enzyme by X-ray crystallography. It is the first reported structure of a 2OGD enzyme involved in coumarin biosynthesis and closely resembles the structure of Arabidopsis thaliana anthocyanidin synthase. To better understand the mechanism of enzyme catalysis and substrate specificity, we also generated a homology model of a related ortho-hydroxylase (C2’H) from sweet potato. By comparing these two structures, we targeted two amino acid residues and verified their roles in substrate binding and specificity by site-directed mutagenesis.

Authors:
 [1];  [2];  [2];  [2];  [1];  [2];  [2];  [2]
+ Show Author Affiliations
  1. Beijing Univ. of Chemical Technology, Beijing (China)
  2. Univ. of Georgia, Athens, GA (United States)
Publication Date:
Research Org.:
Argonne National Laboratory (ANL), Argonne, IL (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES)
OSTI Identifier:
1215409
Grant/Contract Number:  
W-31-109-ENG-38
Resource Type:
Accepted Manuscript
Journal Name:
Scientific Reports
Additional Journal Information:
Journal Volume: 5; Journal ID: ISSN 2045-2322
Publisher:
Nature Publishing Group
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; biocatalysis; enzyme mechanisms; enzymes; X-ray crystallography

Citation Formats

Sun, Xinxiao, Zhou, Dayong, Kandavelu, Palani, Zhang, Hua, Yuan, Qipeng, Wang, Bi -Cheng, Rose, John, and Yan, Yajun. Structural insights into substrate specificity of Feruloyl-CoA 6’-Hydroxylase from Arabidopsis thaliana. United States: N. p., 2015. Web. doi:10.1038/srep10355.
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Sun, Xinxiao, Zhou, Dayong, Kandavelu, Palani, Zhang, Hua, Yuan, Qipeng, Wang, Bi -Cheng, Rose, John, & Yan, Yajun. Structural insights into substrate specificity of Feruloyl-CoA 6’-Hydroxylase from Arabidopsis thaliana. United States. https://doi.org/10.1038/srep10355
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Sun, Xinxiao, Zhou, Dayong, Kandavelu, Palani, Zhang, Hua, Yuan, Qipeng, Wang, Bi -Cheng, Rose, John, and Yan, Yajun. Wed . "Structural insights into substrate specificity of Feruloyl-CoA 6’-Hydroxylase from Arabidopsis thaliana". United States. https://doi.org/10.1038/srep10355. https://www.osti.gov/servlets/purl/1215409.
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@article{osti_1215409,
title = {Structural insights into substrate specificity of Feruloyl-CoA 6’-Hydroxylase from Arabidopsis thaliana},
author = {Sun, Xinxiao and Zhou, Dayong and Kandavelu, Palani and Zhang, Hua and Yuan, Qipeng and Wang, Bi -Cheng and Rose, John and Yan, Yajun},
abstractNote = {Coumarins belong to an important class of plant secondary metabolites. Feruloyl-CoA 6’-hydroxylase (F6’H), a 2-oxoglutarate dependent dioxygenase (2OGD), catalyzes a pivotal step in the biosynthesis of a simple coumarin scopoletin. In this study, we determined the 3-dimensional structure of the F6’H1 apo enzyme by X-ray crystallography. It is the first reported structure of a 2OGD enzyme involved in coumarin biosynthesis and closely resembles the structure of Arabidopsis thaliana anthocyanidin synthase. To better understand the mechanism of enzyme catalysis and substrate specificity, we also generated a homology model of a related ortho-hydroxylase (C2’H) from sweet potato. By comparing these two structures, we targeted two amino acid residues and verified their roles in substrate binding and specificity by site-directed mutagenesis.},
doi = {10.1038/srep10355},
journal = {Scientific Reports},
number = ,
volume = 5,
place = {United States},
year = {Wed May 20 00:00:00 EDT 2015},
month = {Wed May 20 00:00:00 EDT 2015}
}
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https://doi.org/10.1038/srep10355
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Cited by: 16 works
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UCSF Chimera?A visualization system for exploratory research and analysis
journal, January 2004

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  • Journal of Computational Chemistry, Vol. 25, Issue 13
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Structural Basis for the Substrate Specificity of the Feruloyl Esterase Domain of the Cellulosomal Xylanase Z from Clostridium thermocellum †
journal, October 2001

  • Schubot, Florian D.; Kataeva, Irina A.; Blum, David L.
  • Biochemistry, Vol. 40, Issue 42
  • DOI: 10.1021/bi011391c

Fe(II)/α-Ketoglutarate-Dependent Hydroxylases and Related Enzymes
journal, January 2004

  • Hausinger, Robert P.
  • Critical Reviews in Biochemistry and Molecular Biology, Vol. 39, Issue 1
  • DOI: 10.1080/10409230490440541

Biosynthesis of Coumarin and Herniarin in Lavender
journal, September 1962

[20] Processing of X-ray diffraction data collected in oscillation mode
book, January 1997

Atomic Structures of the Human Immunophilin FKBP-12 Complexes with FK506 and Rapamycin
journal, January 1993

  • Van Duyne, Gregory D.; Standaert, Robert F.; Karplus, P. Andrew
  • Journal of Molecular Biology, Vol. 229, Issue 1
  • DOI: 10.1006/jmbi.1993.1012

Kinetic and crystallographic studies on deacetoxycephalosporin C synthase (DAOCS)
journal, May 2001

  • Lee, Hwei-Jen; Lloyd, Matthew D.; Harlos, Karl
  • Journal of Molecular Biology, Vol. 308, Issue 5
  • DOI: 10.1006/jmbi.2001.4649

SWISS-MODEL: modelling protein tertiary and quaternary structure using evolutionary information
journal, April 2014

  • Biasini, Marco; Bienert, Stefan; Waterhouse, Andrew
  • Nucleic Acids Research, Vol. 42, Issue W1
  • DOI: 10.1093/nar/gku340
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