Radical-mediated dehydration reactions in anaerobic bacteria
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Wolfgang Buckel
Abstract
Most dehydratases catalyse the elimination of water from β-hydroxy ketones, β-hydroxy carboxylic acids or β-hydroxyacyl-CoA. The electron-withdrawing carbonyl functionalities acidify the α-hydrogens to enable their removal by basic amino acid side chains. Anaerobic bacteria, however, ferment amino acids via α- or γ-hydroxyacyl-CoA, dehydrations of which involve the abstraction of a β-hydrogen, which is ostensibly non-acidic (pK ca. 40). Evidence is accumulating that β-hydrogens are acidified via transient conversion of the CoA derivatives to enoxy radicals by one-electron transfers, which decrease the pK to 14. The dehydrations of (R)-2-hydroxyacyl-CoA to (E)-2-enoyl-CoA are catalysed by heterodimeric [4Fe-4S]-containing dehydratases, which require reductive activation by an ATP-dependent one-electron transfer mediated by a homodimeric protein with a [4Fe-4S] cluster between the two subunits. The electron is further transferred to the substrate, yielding a ketyl radical anion, which expels the hydroxyl group and forms an enoxy radical. The dehydration of 4-hydroxybutyryl-CoA to crotonyl-CoA involves a similar mechanism, in which the ketyl radical anion is generated by one-electron oxidation. The structure of the FAD- and [4Fe-4S]-containing homotetrameric dehydratase is related to that of acyl-CoA dehydrogenases, suggesting a radical-based mechanism for both flavoproteins.
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Articles in the same Issue
- Highlight: Radicals in Enzymatic Catalysis
- Radical-mediated dehydration reactions in anaerobic bacteria
- Heterodisulfide reductase from methanogenic archaea: a new catalytic role for an iron-sulfur cluster
- Structural and functional comparison of HemN to other radical SAM enzymes
- New glycyl radical enzymes catalysing key metabolic steps in anaerobic bacteria
- Unusual reactions involved in anaerobic metabolism of phenolic compounds
- Novel bacterial molybdenum and tungsten enzymes: three-dimensional structure, spectroscopy, and reaction mechanism
- Spectroscopic and theoretical approaches for studying radical reactions in class I ribonucleotide reductase
- Biomimetic metal-radical reactivity: aerial oxidation of alcohols, amines, aminophenols and catechols catalyzed by transition metal complexes
- Combinatorial approaches to functional models for galactose oxidase
- Spectroscopic characterization of the iron-oxo intermediate in cytochrome P450
- Impact of Mycoplasma hyorhinis infection on l-arginine metabolism: differential regulation of the human and murine iNOS gene
- Degradation of the sodium taurocholate cotransporting polypeptide (NTCP) by the ubiquitin-proteasome system
- Identification of three novel mutations in the dihydropyrimidine dehydrogenase gene associated with altered pre-mRNA splicing or protein function