A New Member of the Thioredoxin Reductase Family from Early Oxygenic Photosynthetic Organisms

Buey, Rubén M.; Galindo-Trigo, Sergio; López‐Maury, Luis; Velázquez‐Campoy, Adrián; Revuelta, José Luis; Florencio, Francisco J.; Pereda, José M. de; Schürmann, Peter; Buchanan, Bob B.; Balsera, Mónica

doi:10.1016/j.molp.2016.06.019

Cited by 16 publications

(26 citation statements)

References 11 publications

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“…Recently, a number of NTR-related flavoproteins have been found to reduce Trx in a pyridine nucleotide-independent manner in both bacteria and archaea (17,32,33). The findings support the view that cells have developed multiple ways to modulate Trx-linked processes during evolution.…”

Section: Discussionsupporting

confidence: 61%

“…1) and phylogenetic analyses ( Fig. S1) of annotated TRs in cyanobacteria clearly distinguish three groups of NTR-related enzymes: the archetypal NTR (and the related NTRC), the recently characterized NADP-independent DTR (17), and a third uncharacterized group herein named DDOR or diflavin-linked disulfide oxidoreductase (see below).…”

Section: Resultsmentioning

confidence: 96%

“…2C). This behavior contrasted with Escherichia coli NTR (EcNTR) and GvDTR, whose flavins were reduced by DTH without the accumulation of SQ intermediates in a reaction quickly reversed by Trx addition (17,20). These results provided evidence that the GvDDOR flavoprotein is not a TR.…”

Section: Resultsmentioning

confidence: 97%

“…organisms, including an enzyme called "DTR" (for "deeplyrooted thioredoxin reductase") that reduces Trxs in a pyridine nucleotide-independent manner. DTR is present in some cyanobacteria and marine algae (17), but the physiological electron donor has not been identified.…”

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confidence: 99%

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Unprecedented pathway of reducing equivalents in a diflavin-linked disulfide oxidoreductase

Buey¹,

Arellano²,

López‐Maury³

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Flavoproteins participate in a wide variety of physiologically relevant processes that typically involve redox reactions. Within this protein superfamily, there exists a group that is able to transfer reducing equivalents from FAD to a redox-active disulfide bridge, which further reduces disulfide bridges in target proteins to regulate their structure and function. We have identified a previously undescribed type of flavin enzyme that is exclusive to oxygenic photosynthetic prokaryotes and that is based on the primary sequence that had been assigned as an NADPH-dependent thioredoxin reductase (NTR). However, our experimental data show that the protein does not transfer reducing equivalents from flavins to disulfides as in NTRs but functions in the opposite direction. High-resolution structures of the protein from and sp. PCC6803 obtained by X-ray crystallography showed two juxtaposed FAD molecules per monomer in redox communication with an active disulfide bridge in a variant of the fold adopted by NTRs. We have tentatively named the flavoprotein "DDOR" (diflavin-linked disulfide oxidoreductase) and propose that its activity is linked to a thiol-based transfer of reducing equivalents in bacterial membranes. These findings expand the structural and mechanistic repertoire of flavoenzymes with oxidoreductase activity and pave the way to explore new protein engineering approaches aimed at designing redox-active proteins for diverse biotechnological applications.

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Section: Discussionsupporting

confidence: 61%

Section: Resultsmentioning

confidence: 96%

Section: Resultsmentioning

confidence: 97%

mentioning

confidence: 99%

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Unprecedented pathway of reducing equivalents in a diflavin-linked disulfide oxidoreductase

Buey¹,

Arellano²,

López‐Maury³

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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“…Another surprise is offered by the flavin-containing TrxR of T. acidophilum, an anaerobic archaeon, where the EЈ 0 of the protein-bound FAD is Ϫ305 mV, and yet the enzyme cannot use NAD(P)H as a reductant (65). A recent report describes a TrxR from an aerobic cyanobacterium that is a close structural homolog of NTR and cannot use nicotinamides (66). The overall situation is reminiscent of the enolase superfamily, where few changes within a generally conserved active site have allowed transformation of a diversity of substrates (67).…”

Section: Discussionmentioning

confidence: 99%

A Novel F420-dependent Thioredoxin Reductase Gated by Low Potential FAD

Susanti¹,

Loganathan²,

Mukhopadhyay

2016

Journal of Biological Chemistry

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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 flavincontaining NADPH-dependent TrxRs (NTR), lacked an NADPH-binding site and was dependent on reduced coenzyme F 420 (F 420 H 2 ), a stronger reductant with a mid-point redox potential (E 0 ) of ؊360 mV; E 0 of NAD(P)H is ؊320 mV. Because F 420 is a deazaflavin, this enzyme was named deazaflavin-dependent flavin-containing thioredoxin reductase (DFTR). It transferred electrons from F 420 H 2 to thioredoxin via proteinbound flavin; K m values for thioredoxin and F 420 H 2 were 6.3 and 28.6 M, respectively. The E 0 of DFTR-bound flavin was approximately ؊389 mV, making electron transfer from NAD(P)H or F 420 H 2 to flavin endergonic. However, under high partial pressures of hydrogen prevailing on early Earth and present day deep-sea volcanoes, the potential for the F 420 /F 420 H 2 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 F 420 -dependent enzyme (DFTR) and an NADPH-dependent enzyme (NTR) brought new thoughts to investigations on F 420 systems involved in microbial pathogenesis and antibiotic production.

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Overview of structurally homologous flavoprotein oxidoreductases containing the low Mr thioredoxin reductase-like fold – A functionally diverse group

Hammerstad

Hersleth

2021

Archives of Biochemistry and Biophysics

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A New Member of the Thioredoxin Reductase Family from Early Oxygenic Photosynthetic Organisms

Cited by 16 publications

References 11 publications

Unprecedented pathway of reducing equivalents in a diflavin-linked disulfide oxidoreductase

Unprecedented pathway of reducing equivalents in a diflavin-linked disulfide oxidoreductase

A Novel F420-dependent Thioredoxin Reductase Gated by Low Potential FAD

Overview of structurally homologous flavoprotein oxidoreductases containing the low Mr thioredoxin reductase-like fold – A functionally diverse group

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