title: One-carbon chemistry of oxalate oxidoreductase captured by X-ray crystallography.
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.
authors.affiliation: Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139;
authors.forename: Marcus I
authors.identifier: http://orcid.org/0000-0003-0788-5510
authors.initials: MI
authors.lastname: Gibson
authors.affiliation: Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139;
authors.forename: Percival Yang-Ting
authors.initials: PY
authors.lastname: Chen
authors.affiliation: Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139;
authors.forename: Aileen C
authors.initials: AC
authors.lastname: Johnson
authors.affiliation: Department of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109;
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Pierce
authors.affiliation: Department of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109;
authors.forename: Mehmet
authors.initials: M
authors.lastname: Can
authors.affiliation: Department of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109;
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Ragsdale
authors.affiliation: Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139; Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139 cdrennan@mit.edu.
authors.forename: Catherine L
authors.initials: CL
authors.lastname: Drennan
mesh_terms: D002244:Carbon / Q000378:metabolism*; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D058845:Moorella / Q000201:enzymology*; D010070:Oxalates / Q000378:metabolism; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000737:chemistry / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D012997:Solvents
chemical_list: D010070:Oxalates; D012997:Solvents; D002244:Carbon; D010088:Oxidoreductases
keywords: carbon dioxide; oxalate; oxidoreductase; thiamine pyrophosphate