1qhm
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ESCHERICHIA COLI PYRUVATE FORMATE LYASE LARGE DOMAIN
OverviewOverview
BACKGROUND: Pyruvate formate lyase (PFL) catalyses a key step in, Escherichia coli anaerobic glycolysis by converting pyruvate and CoA to, formate and acetylCoA. The PFL mechanism involves an unusual radical, cleavage of pyruvate, involving an essential C alpha radical of Gly734 and, two cysteine residues, Cys418 and Cys419, which may form thiyl radicals, required for catalysis. We undertook this study to understand the, structural basis for catalysis. RESULTS: The first structure of a fragment, of PFL (residues 1-624) at 2.8 A resolution shows an unusual barrel-like, structure, with a catalytic beta finger carrying Cys418 and Cys419, inserted into the centre of the barrel. Several residues near the, active-site cysteines can be ascribed roles in the catalytic mechanism:, Arg176 and Arg435 are positioned near Cys419 and may bind pyruvate/formate, and Trp333 partially buries Cys418. Both cysteine residues are accessible, to each other owing to their cis relationship at the tip of the beta, finger. Finally, two clefts that may serve as binding sites for CoA and, pyruvate have been identified. CONCLUSIONS: PFL has striking structural, homology to the aerobic ribonucleotide reductase (RNR): the superposition, of PFL and RNR includes eight of the ten strands in the unusual RNR, alpha/beta barrel as well as the beta finger, which carries key catalytic, residues in both enzymes. This provides the first structural proof that, RNRs and PFLs are related by divergent evolution from a common ancestor.
About this StructureAbout this Structure
1QHM is a Single protein structure of sequence from Escherichia coli. Active as Formate C-acetyltransferase, with EC number 2.3.1.54 Full crystallographic information is available from OCA.
ReferenceReference
Pyruvate formate lyase is structurally homologous to type I ribonucleotide reductase., Leppanen VM, Merckel MC, Ollis DL, Wong KK, Kozarich JW, Goldman A, Structure. 1999 Jul 15;7(7):733-44. PMID:10425676
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