title: The Structure of an Oxalate Oxidoreductase Provides Insight into Microbial 2-Oxoacid Metabolism.
abstract: Thiamine pyrophosphate (TPP), a derivative of vitamin B1, is a versatile and ubiquitous cofactor. When coupled with [4Fe-4S] clusters in microbial 2-oxoacid:ferredoxin oxidoreductases (OFORs), TPP is involved in catalyzing low-potential redox reactions that are important for the synthesis of key metabolites and the reduction of N2, H(+), and CO2. We have determined the high-resolution (2.27 Å) crystal structure of the TPP-dependent oxalate oxidoreductase (OOR), an enzyme that allows microbes to grow on oxalate, a widely occurring dicarboxylic acid that is found in soil and freshwater and is responsible for kidney stone disease in humans. OOR catalyzes the anaerobic oxidation of oxalate, harvesting the low-potential electrons for use in anaerobic reduction and fixation of CO2. We compare the OOR structure to that of the only other structurally characterized OFOR family member, pyruvate:ferredoxin oxidoreductase. This side-by-side structural analysis highlights the key similarities and differences that are relevant for the chemistry of this entire class of TPP-utilizing enzymes.
authors.affiliation: †Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States.
authors.forename: Marcus I
authors.initials: MI
authors.lastname: Gibson
authors.affiliation: †Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States.|‡Howard Hughes Medical Institute, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States.
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Brignole
authors.affiliation: §Department of Biological Chemistry, University of Michigan, Ann Arbor, Michigan 48109, United States.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Pierce
authors.affiliation: §Department of Biological Chemistry, University of Michigan, Ann Arbor, Michigan 48109, United States.
authors.forename: Mehmet
authors.initials: M
authors.lastname: Can
authors.affiliation: §Department of Biological Chemistry, University of Michigan, Ann Arbor, Michigan 48109, United States.
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Ragsdale
authors.affiliation: †Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States.|‡Howard Hughes Medical Institute, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States.|∥Department of Biology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States.
authors.forename: Catherine L
authors.initials: CL
authors.lastname: Drennan
mesh_terms: D008958:Models, Molecular; D058845:Moorella / Q000737:chemistry / Q000201:enzymology* / Q000378:metabolism*; D010070:Oxalates / Q000378:metabolism*; D010088:Oxidoreductases / Q000737:chemistry* / Q000378:metabolism*; D011487:Protein Conformation; D013835:Thiamine Pyrophosphate / Q000378:metabolism
chemical_list: D010070:Oxalates; D010088:Oxidoreductases; D013835:Thiamine Pyrophosphate