Pyruvate formate lyase is structurally homologous to type I ribonucleotide reductase
| Autor: | David L. Ollis, John W. Kozarich, Adrian Goldman, Veli-Matti Leppänen, Kenny K. Wong, Michael C Merckel |
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| Rok vydání: | 1999 |
| Předmět: |
Models
Molecular Protein Conformation Stereochemistry Molecular Sequence Data Crystallography X-Ray ribonucleotide reductase chemistry.chemical_compound Acetyltransferases Structural Biology Ribonucleotide Reductases enzyme mechanism Formate Amino Acid Sequence structure Binding site Molecular Biology X-ray crystallography chemistry.chemical_classification Chemistry Lyase Enzyme structure Enzyme binding Enzyme Ribonucleotide reductase Biochemistry pyruvate formate lyase Cysteine |
| Zdroj: | Structure. 7:733-744 |
| ISSN: | 0969-2126 |
| DOI: | 10.1016/s0969-2126(99)80098-7 |
| Popis: | 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 α 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 2.8A resolution shows an unusual barrel-like structure, with a catalytic β 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 β 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 α / β barrel as well as the β 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. |
| Databáze: | OpenAIRE |
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