Structure and Function of 4-Hydroxyphenylacetate Decarboxylase and Its Cognate Activating Enzyme

Selvaraj, Brinda; Golding, BT; Ullmann, G. Matthias; Martins, BM

doi:10.1159/000440882

Cited by 19 publications

(14 citation statements)

References 52 publications

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“…5a). 25 Biochemical experiments and sequence analysis of hydroxyphenylacetate decarboxylase activating enzyme by Selvaraj et al 25 support this. Anaerobic reconstitution of the IseH [4Fe-4S] clusters resulted in 5.9 ± 0.1 Fe and 8.4 ± 0.1 S per monomer (out of the theoretical maximum of 12 Fe and 12 S) (Supplementary Fig.…”

Section: Resultsmentioning

confidence: 94%

Radical-mediated C-S bond cleavage in C2 sulfonate degradation by anaerobic bacteria

et al. 2019

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Bacterial degradation of organosulfonates plays an important role in sulfur recycling, and has been extensively studied. However, this process in anaerobic bacteria especially gut bacteria is little known despite of its potential significant impact on human health with the production of toxic H 2 S. Here, we describe the structural and biochemical characterization of an oxygen-sensitive enzyme that catalyzes the radical-mediated C-S bond cleavage of isethionate to form sulfite and acetaldehyde. We demonstrate its involvement in pathways that enables C2 sulfonates to be used as terminal electron acceptors for anaerobic respiration in sulfate- and sulfite-reducing bacteria. Furthermore, it plays a key role in converting bile salt-derived taurine into H 2 S in the disease-associated gut bacterium Bilophila wadsworthia . The enzymes and transporters in these anaerobic pathways expand our understanding of microbial sulfur metabolism, and help deciphering the complex web of microbial pathways involved in the transformation of sulfur compounds in the gut.

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Section: Resultsmentioning

confidence: 94%

Radical-mediated C-S bond cleavage in C2 sulfonate degradation by anaerobic bacteria

et al. 2019

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“…The sequence of OsIADAE contains a conserved CX 2 CX 3 C motif that coordinates the radical SAM [4Fe-4S] cluster 22 , 30 , as well as a 8-cysteine motif thought to coordinate two auxiliary [4Fe-4S] clusters in a ferredoxin-like domain present in many GRE-activating enzymes (Supplementary Fig. 2 ) 31 . Anaerobic reconstitution of OsIADAE resulted in 6.5 ± 0.1 Fe and 7.9 ± 0.2 S per monomer (out of a theoretical 12 Fe and 12 S for one radical SAM and two auxiliary [4Fe-4S] clusters) (Supplementary Fig.…”

Section: Resultsmentioning

confidence: 99%

Indoleacetate decarboxylase is a glycyl radical enzyme catalysing the formation of malodorant skatole

et al. 2018

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Skatole is a malodorous compound that contributes to the characteristic smell of animal faeces. Although skatole has long been known to originate from bacterial tryptophan fermentation, the enzyme catalysing its formation has so far remained elusive. Here we report the use of comparative genomics for the discovery of indoleacetate decarboxylase, an O2-sensitive glycyl radical enzyme catalysing the decarboxylation of indoleacetate to form skatole as the terminal step of tryptophan fermentation in certain anaerobic bacteria. We describe its biochemical characterization and compare it to other glycyl radical decarboxylases. Indoleacetate decarboxylase may serve as a genetic marker for the identification of skatole-producing environmental and human-associated bacteria, with impacts on human health and the livestock industry.

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“…HPAD, which has been the subject of a recent review (Selvaraj et al , 2016), cleaves the tyrosine-derived metabolite 4-hydroxyphenylacetate to p -cresol and carbon dioxide (D’Ari and Barker, 1985, Selmer and Andrei, 2001). p -cresol is thought to promote virulence of Clostridium difficile and related pathogens (Dawson et al , 2008).…”

Section: Gre Ribonucleotide Reductasesmentioning

confidence: 99%

New tricks for the glycyl radical enzyme family

Backman

Funk

Dawson

et al. 2017

Critical Reviews in Biochemistry and Molecular Biology

129

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Glycyl radical enzymes (GREs) are important biological catalysts in both strict and facultative anaerobes, playing key roles both in the human microbiota and in the environment. GREs contain a backbone glycyl radical that is post-translationally installed, enabling radical-based mechanisms. GREs function in several metabolic pathways including mixed acid fermentation, ribonucleotide reduction, and the anaerobic breakdown of the nutrient choline and the pollutant toluene. By generating a substrate-based radical species within the active site, GREs enable C-C, C-O, and C-N bond breaking and formation steps that are otherwise challenging for non-radical enzymes. Identification of previously unknown family members from genomic data and the determination of structures of well-characterized GREs have expanded the scope of GRE-catalyzed reactions as well as defined key features that enable radical catalysis. Here we review the structures and mechanisms of characterized GREs, classifying members into five categories. We consider the open questions about each of the five GRE classes and evaluate the tools available to interrogate uncharacterized GREs.

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Structure and Function of 4-Hydroxyphenylacetate Decarboxylase and Its Cognate Activating Enzyme

Cited by 19 publications

References 52 publications

Radical-mediated C-S bond cleavage in C2 sulfonate degradation by anaerobic bacteria

Radical-mediated C-S bond cleavage in C2 sulfonate degradation by anaerobic bacteria

Indoleacetate decarboxylase is a glycyl radical enzyme catalysing the formation of malodorant skatole

New tricks for the glycyl radical enzyme family

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