6cin
Crystal structure of pyruvate:ferredoxin oxidoreductase from Moorella thermoaceticaCrystal structure of pyruvate:ferredoxin oxidoreductase from Moorella thermoacetica
Structural highlights
FunctionPFOR_MOOTA Catalyzes the oxidative decarboxylation of pyruvate to acetyl-CoA and carbon dioxide. The two electrons that are generated as a result of pyruvate decarboxylation are used in the reduction of low potential ferredoxins, which provide reducing equivalents for central metabolism. Also catalyzes the reverse reaction, i.e. the synthesis of pyruvate from acetyl-CoA and carbon dioxide. Appears to function physiologically in both directions (PubMed:10878009). The oxidation of pyruvate by PFOR is required to connect glycolysis and the Wood-Ljungdahl pathway of reductive acetogenesis. The conversion of acetyl-CoA to pyruvate links the Wood-Ljungdahl pathway of autotrophic CO2 fixation to the reductive tricarboxylic acid cycle (PubMed:10878009, PubMed:29581263). Can use methyl viologen as electron carrier in vitro (PubMed:9214293, PubMed:29581263).[1] [2] [3] [4] [5] Publication Abstract from PubMedPyruvate:ferredoxin oxidoreductase (PFOR) is a microbial enzyme that uses thiamine pyrophosphate (TPP), three [4Fe-4S] clusters, and coenzyme A (CoA) in the reversible oxidation of pyruvate to generate acetyl-CoA and carbon dioxide. The two electrons that are generated as a result of pyruvate decarboxylation are used in the reduction of low potential ferredoxins, which provide reducing equivalents for central metabolism, including the Wood-Ljungdahl pathway. PFOR is a member of the 2-oxoacid:ferredoxin oxidoreductase (OFOR) superfamily, which plays major roles in both microbial redox reactions and carbon dioxide fixation. Here, we present a set of crystallographic snapshots of the best-studied member of this superfamily, the PFOR from Moorella thermoacetica (MtPFOR). These snapshots include the native structure, those of lactyl-TPP and acetyl-TPP reaction intermediates, and the first of an OFOR with CoA bound. These structural data reveal the binding site of CoA as domain III, the function of which in OFORs was previously unknown, and establish sequence motifs for CoA binding in the OFOR superfamily. MtPFOR structures further show that domain III undergoes a conformational change upon CoA binding that seals off the active site and positions the thiolate of CoA directly adjacent to the TPP cofactor. These structural findings provide a molecular basis for the experimental observation that CoA binding accelerates catalysis by 10(5)-fold. Binding site for coenzyme A revealed in the structure of pyruvate:ferredoxin oxidoreductase from Moorella thermoacetica.,Chen PY, Aman H, Can M, Ragsdale SW, Drennan CL Proc Natl Acad Sci U S A. 2018 Mar 26. pii: 1722329115. doi:, 10.1073/pnas.1722329115. PMID:29581263[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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