6GNA

Crystal structure of a Ferredoxin-Flavin Thioredoxin Reductase from Clostridium acetobutylicum at 1.3 A resolution

Summary for 6GNA

• Entry DOI: 10.2210/pdb6gna/pdb
• Descriptor: Thioredoxin reductase, FLAVIN-ADENINE DINUCLEOTIDE, TRIETHYLENE GLYCOL, ... (6 entities in total)
• Functional Keywords: flavoprotein, thioredoxin reductase, oxidoreductase
• Biological source: Clostridium acetobutylicum ATCC 824
• Total number of polymer chains: 1
• Total formula weight: 33229.74

Authors

Buey, R.M.,Fernandez-Justel, D.,Balsera, M. (deposition date: 2018-05-30, release date: 2018-12-12, Last modification date: 2024-01-17)

Primary citation

Buey, R.M.,Fernandez-Justel, D.,de Pereda, J.M.,Revuelta, J.L.,Schurmann, P.,Buchanan, B.B.,Balsera, M.
Ferredoxin-linked flavoenzyme defines a family of pyridine nucleotide-independent thioredoxin reductases.
Proc. Natl. Acad. Sci. U.S.A., 115:12967-12972, 2018

PubMed Abstract: Ferredoxin-dependent thioredoxin reductase was identified 35 y ago in the fermentative bacterium [Hammel KE, Cornwell KL, Buchanan BB (1983) 80:3681-3685]. The enzyme, a flavoprotein, was strictly dependent on ferredoxin as reductant and was inactive with either NADPH or NADH. This early work has not been further pursued. We have recently reinvestigated the problem and confirmed that the enzyme, here designated ferredoxin-dependent flavin thioredoxin reductase (FFTR), is a flavoprotein. The enzyme differs from ferredoxin-thioredoxin reductase (FTR), which has a signature [4Fe-4S] cluster, but shows structural similarities to NADP-dependent thioredoxin reductase (NTR). Comparative amino acid sequence analysis showed that FFTR is present in a number of clostridial species, some of which lack both FTR and an archetypal NTR. We have isolated, crystallized, and determined the structural properties of FFTR from a member of this group, , both alone and in complex with Trx. The structures showed an elongated FFTR homodimer, each monomer comprising two Rossmann domains and a noncovalently bound FAD cofactor that exposes the isoalloxazine ring to the solvent. The FFTR structures revealed an alternative domain organization compared with NTR that enables the enzyme to accommodate Fdx rather than NADPH. The results suggest that FFTR exists in a range of conformations with varying degrees of domain separation in solution and that the stacking between the two redox-active groups for the transfer of reducing equivalents results in a profound structural reorganization. A mechanism in accord with the findings is proposed.

PubMed: 30510005
DOI: 10.1073/pnas.1812781115

Experimental method

X-RAY DIFFRACTION (1.295 Å)