The Structure of an Oxalate Oxidoreductase Provides Insight into Microbial 2-Oxoacid Metabolism
Author(s)Pierce, Elizabeth; Can, Mehmet; Ragsdale, Stephen W.; Gibson, Marcus Ian; Brignole, Edward J.; Drennan, Catherine L.; ... Show more Show less
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Thiamine pyrophosphate (TPP), a derivative of vitamin B[subfield 1], 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 N[subfield 2], H[superscript +], and CO[subfield 2]. 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 CO[subfield 2]. 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.
DepartmentMassachusetts Institute of Technology. Department of Biology; Massachusetts Institute of Technology. Department of Chemistry
American Chemical Society (ACS)
Gibson, Marcus I., Edward J. Brignole, Elizabeth Pierce, Mehmet Can, Stephen W. Ragsdale, and Catherine L. Drennan. "The Structure of an Oxalate Oxidoreductase Provides Insight into Microbial 2-Oxoacid Metabolism." Biochemistry 54:26 (2015), pp. 4112-4120. © 2015 American Chemical Society.
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