A Novel F420-dependent Thioredoxin Reductase Gated by Low Potential FAD
| Autor: | Usha Loganathan, Dwi Susanti, Biswarup Mukhopadhyay |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
chemistry.chemical_classification Flavin adenine dinucleotide Thioredoxin reductase 030106 microbiology Cell Biology Flavin group Biology Biochemistry Coenzyme F420 03 medical and health sciences chemistry.chemical_compound chemistry Oxidoreductase Thioredoxin-Disulfide Reductase NAD+ kinase Thioredoxin Molecular Biology |
| Zdroj: | Journal of Biological Chemistry. 291:23084-23100 |
| ISSN: | 0021-9258 |
| Popis: | A recent report suggested that the thioredoxin-dependent metabolic regulation, which is widespread in all domains of life, existed in methanogenic archaea about 3.5 billion years ago. We now show that the respective electron delivery enzyme (thioredoxin reductase, TrxR), although structurally similar to flavin-containing NADPH-dependent TrxRs (NTR), lacked an NADPH-binding site and was dependent on reduced coenzyme F420 (F420H2), a stronger reductant with a mid-point redox potential (E'0) of -360 mV; E'0 of NAD(P)H is -320 mV. Because F420 is a deazaflavin, this enzyme was named deazaflavin-dependent flavin-containing thioredoxin reductase (DFTR). It transferred electrons from F420H2 to thioredoxin via protein-bound flavin; Km values for thioredoxin and F420H2 were 6.3 and 28.6 μm, respectively. The E'0 of DFTR-bound flavin was approximately -389 mV, making electron transfer from NAD(P)H or F420H2 to flavin endergonic. However, under high partial pressures of hydrogen prevailing on early Earth and present day deep-sea volcanoes, the potential for the F420/F420H2 pair could be as low as -425 mV, making DFTR efficient. The presence of DFTR exclusively in ancient methanogens and mostly in the early Earth environment of deep-sea volcanoes and DFTR's characteristics suggest that the enzyme developed on early Earth and gave rise to NTR. A phylogenetic analysis revealed six more novel-type TrxR groups and suggested that the broader flavin-containing disulfide oxidoreductase family is more diverse than previously considered. The unprecedented structural similarities between an F420-dependent enzyme (DFTR) and an NADPH-dependent enzyme (NTR) brought new thoughts to investigations on F420 systems involved in microbial pathogenesis and antibiotic production. |
| Databáze: | OpenAIRE |
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