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

Journal Article · · Proceedings of the National Academy of Sciences of the United States of America
ORCiD logo [1];  [2];  [3];  [4];  [5];  [5];  [2]
  1. Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States); Princeton Univ., NJ (United States)
  2. Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States)
  3. Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States); Emory Univ. School of Medicine, Atlanta, GA (United States)
  4. Univ. of Michigan, Ann Arbor, MI (United States); Southern Utah Univ., Cedar City, UT (United States)
  5. Univ. of Michigan, Ann Arbor, MI (United States)
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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. Furthermore, 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.

Research Organization:
Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Organization:
National Institutes of Health (NIH); USDOE Office of Science (SC), Basic Energy Sciences (BES). Scientific User Facilities Division
Grant/Contract Number:
GM069857; GM39451; 1122374; P41 GM103403; AC02-06CH11357
OSTI ID:
1235478
Journal Information:
Proceedings of the National Academy of Sciences of the United States of America, Vol. 113, Issue 2; ISSN 0027-8424
Publisher:
National Academy of SciencesCopyright Statement
Country of Publication:
United States
Language:
ENGLISH
Citation Metrics:
Cited by: 11 works
Citation information provided by
Web of Science

References (30)

Flexibility of Thiamine Diphosphate Revealed by Kinetic Crystallographic Studies of the Reaction of Pyruvate-Ferredoxin Oxidoreductase with Pyruvate journal February 2006
Bacillus subtilis YvrK Is an Acid-Induced Oxalate Decarboxylase journal January 2000
Isolation and analysis of the gene encoding the pyruvate-ferredoxin oxidoreductase of Desulfovibrio africanus, production of the recombinant enzyme in Escherichia coli, and effect of carboxy-terminal deletions on its stability. journal September 1997
On the Mechanism of Thiamine Action. IV. 1 Evidence from Studies on Model Systems journal July 1958
EPR Spectroscopic and Computational Characterization of the Hydroxyethylidene-Thiamine Pyrophosphate Radical Intermediate of Pyruvate:Ferredoxin Oxidoreductase † journal June 2006
The Roles of Coenzyme A in the Pyruvate:Ferredoxin Oxidoreductase Reaction Mechanism:  Rate Enhancement of Electron Transfer from a Radical Intermediate to an Iron−Sulfur Cluster † journal August 2002
Oxalate Oxidase from Barley Roots: Purification to Homogeneity and Study of Some Molecular, Catalytic, and Binding Properties journal April 1997
Oxalate in renal stone disease: the terminal metabolite that just won't go away journal June 2008
Radical reactions of thiamin pyrophosphate in 2-oxoacid oxidoreductases journal November 2012
Oxalobacter formigenes gen. nov., sp. nov.: oxalate-degrading anaerobes that inhabit the gastrointestinal tract journal February 1985
Catalysis of decarboxylation by an adjacent negative charge: a theoretical approach journal August 2003
Pyruvate Ferredoxin Oxidoreductase and Its Radical Intermediate † journal June 2003
Oxalate metabolism by the acetogenic bacterium Moorella thermoacetica journal February 2004
Oxalate production by fungi: its role in pathogenicity and ecology in the soil environment journal September 1996
Carbon Assimilation by Pseudomonas Oxalaticus (ox 1). 7. Decarboxylation of Oxalyl-Coenzyme a to Formyl-Coenzyme a journal December 1963
Pulsed Electron Paramagnetic Resonance Experiments Identify the Paramagnetic Intermediates in the Pyruvate Ferredoxin Oxidoreductase Catalytic Cycle journal March 2006
Characterization of a fourth type of 2-keto acid-oxidizing enzyme from a hyperthermophilic archaeon: 2-ketoglutarate ferredoxin oxidoreductase from Thermococcus litoralis. journal October 1996
Calcium Oxalate Microcrystalline-Associated Arthritis in End-Stage Renal Disease journal July 1982
Physical organic chemistry of benzisoxazoles. IV. Origins and catalytic nature of the solvent rate acceleration for the decarboxylation of 3-carboxybenzisoxazoles journal December 1975
Molecular and phylogenetic characterization of pyruvate and 2-ketoisovalerate ferredoxin oxidoreductases from Pyrococcus furiosus and pyruvate ferredoxin oxidoreductase from Thermotoga maritima. journal January 1996
The crystal structure and mechanism of orotidine 5'-monophosphate decarboxylase journal February 2000
Isolation and characterization of the pyruvate-ferredoxin oxidoreductase from the sulfate-reducing bacterium Desulfovibrio africanus journal July 1995
Crystal Structure of the Free Radical Intermediate of Pyruvate:Ferredoxin Oxidoreductase journal December 2001
Oxalate- and Glyoxylate-Dependent Growth and Acetogenesis by Clostridium thermoaceticum journal January 1993
The Structure of an Oxalate Oxidoreductase Provides Insight into Microbial 2-Oxoacid Metabolism journal June 2015
The Role of Pyruvate Ferredoxin Oxidoreductase in Pyruvate Synthesis during Autotrophic Growth by the Wood-Ljungdahl Pathway journal June 2000
Identification and Characterization of Oxalate Oxidoreductase, a Novel Thiamine Pyrophosphate-dependent 2-Oxoacid Oxidoreductase That Enables Anaerobic Growth on Oxalate journal October 2010
An Unusual Role for a Mobile Flavin in StaC-like Indolocarbazole Biosynthetic Enzymes journal July 2012
Oxalate:formate exchange journal May 1989
Pyruvoyl-dependent Histidine Decarboxylase journal July 1989

Cited By (5)

X-ray crystallography–based structural elucidation of enzyme-bound intermediates along the 1-deoxy-d-xylulose 5-phosphate synthase reaction coordinate journal June 2019
Crystal structures of archaeal 2-oxoacid:ferredoxin oxidoreductases from Sulfolobus tokodaii journal September 2016
Binding site for coenzyme A revealed in the structure of pyruvate:ferredoxin oxidoreductase from Moorella thermoacetica journal March 2018
Anaerobic Radical Enzymes for Biotechnology journal April 2018
Kinetics and mechanistic study of the reduction of $$\hbox {Mn}^{\mathrm{III}}$$ Mn III by oxalate in Salophen scaffold: relevance to oxalate oxidase journal August 2018

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Related Subjects

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
oxalate
oxidoreductase
carbon dioxide
thiamine pyrophosphate