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Research Article

One-carbon chemistry of oxalate oxidoreductase captured by X-ray crystallography

View ORCID ProfileMarcus I. Gibson, Percival Yang-Ting Chen, Aileen C. Johnson, Elizabeth Pierce, Mehmet Can, Stephen W. Ragsdale, and Catherine L. Drennan
PNAS January 12, 2016 113 (2) 320-325; first published December 28, 2015; https://doi.org/10.1073/pnas.1518537113
Marcus I. Gibson
aDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139;
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  • ORCID record for Marcus I. Gibson
Percival Yang-Ting Chen
aDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139;
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Aileen C. Johnson
aDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139;
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Elizabeth Pierce
bDepartment of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109;
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Mehmet Can
bDepartment of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109;
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Stephen W. Ragsdale
bDepartment of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109;
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Catherine L. Drennan
aDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139;
cHoward Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139;
dDepartment of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139
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  • For correspondence: cdrennan@mit.edu
  1. Edited by Gregory A. Petsko, Weill Cornell Medical College, New York, NY, and approved November 30, 2015 (received for review September 21, 2015)

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Significance

The microbial Wood−Ljungdahl pathway is the biological equivalent of the Monsanto process, responsible for converting greenhouse gas CO2 into acetate. In addition to CO2, this microbial pathway requires low-potential electrons. The recently discovered oxalate oxidoreductase produces both low-potential electrons and CO2 through the oxidation of oxalate. Here our structural data allow us to visualize intermediates along the reaction cycle that have not been previously described, providing insight into the molecular mechanism by which oxalate is metabolized.

Abstract

Thiamine pyrophosphate (TPP)-dependent oxalate oxidoreductase (OOR) metabolizes oxalate, generating two molecules of CO2 and two low-potential electrons, thus providing both the carbon and reducing equivalents for operation of the Wood−Ljungdahl pathway of acetogenesis. Here we present structures of OOR in which two different reaction intermediate bound states have been trapped: the covalent adducts between TPP and oxalate and between TPP and CO2. These structures, along with the previously determined structure of substrate-free OOR, allow us to visualize how active site rearrangements can drive catalysis. Our results suggest that OOR operates via a bait-and-switch mechanism, attracting substrate into the active site through the presence of positively charged and polar residues, and then altering the electrostatic environment through loop and side chain movements to drive catalysis. This simple but elegant mechanism explains how oxalate, a molecule that humans and most animals cannot break down, can be used for growth by acetogenic bacteria.

  • oxalate
  • oxidoreductase
  • carbon dioxide
  • thiamine pyrophosphate

Footnotes

  • ↵1Present address: Department of Chemistry, Princeton University, Princeton, NJ 08540.

  • ↵2Present address: Emory University School of Medicine, Atlanta, GA 30307.

  • ↵3Present address: Physical Science Department, Southern Utah University, Cedar City, UT 84720.

  • ↵4To whom correspondence should be addressed. Email: cdrennan{at}mit.edu.
  • Author contributions: M.I.G., S.W.R., and C.L.D. designed research; M.I.G., P.Y.-T.C., A.C.J., E.P., and M.C. performed research; M.I.G., P.Y.-T.C., S.W.R., and C.L.D. analyzed data; and M.I.G. and C.L.D. wrote the paper.

  • The authors declare no conflict of interest.

  • This article is a PNAS Direct Submission.

  • Data deposition: The atomic coordinates have been deposited in the Protein Data Bank, www.pdb.org (PDB ID codes 5EXD and 5EXE).

  • This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1518537113/-/DCSupplemental.

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Structures of the one-carbon chemistry of OOR
Marcus I. Gibson, Percival Yang-Ting Chen, Aileen C. Johnson, Elizabeth Pierce, Mehmet Can, Stephen W. Ragsdale, Catherine L. Drennan
Proceedings of the National Academy of Sciences Jan 2016, 113 (2) 320-325; DOI: 10.1073/pnas.1518537113

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Structures of the one-carbon chemistry of OOR
Marcus I. Gibson, Percival Yang-Ting Chen, Aileen C. Johnson, Elizabeth Pierce, Mehmet Can, Stephen W. Ragsdale, Catherine L. Drennan
Proceedings of the National Academy of Sciences Jan 2016, 113 (2) 320-325; DOI: 10.1073/pnas.1518537113
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