Thiosulfate dehydrogenase

 

Thiosulphate dehydrogenase (TsdA) catalyses the oxidation of two thiosulphate molecules to form tetrathionate and is predicted to use an unusual cysteine-ligated heme as the catalytic cofactor. Thiosulfate and polythionates serve as energy-yielding or electron-donating substrates in the metabolism of a wide range of chemolithotrophic and photolithotrophic bacteria, as well as some heterotrophs. This reaction is interesting because of its potential applications in bioleaching and metal solubilisation.

 

Reference Protein and Structure

Sequence
D3RVD4 UniProt (1.8.2.2) IPR036909 (Sequence Homologues) (PDB Homologues)
Biological species
Allochromatium vinosum DSM 180 (Bacteria) Uniprot
PDB
4v2k - Crystal structure of the thiosulfate dehydrogenase TsdA in complex with thiosulfate (1.29 Å) PDBe PDBsum 4v2k
Catalytic CATH Domains
1.10.760.10 CATHdb (see all for 4v2k)
Click To Show Structure

Enzyme Reaction (EC:1.8.2.2)

iron(3+)
CHEBI:29034ChEBI
+
trioxidosulfanidosulfate(1-)
CHEBI:33542ChEBI
→
iron(2+)
CHEBI:29033ChEBI
+
hydron
CHEBI:15378ChEBI
+
tetrathionate(2-)
CHEBI:15226ChEBI
Alternative enzyme names: Tetrathionate synthase, Thiosulfate oxidase, Thiosulfate-acceptor oxidoreductase, Thiosulfate-oxidizing enzyme, TsdA (gene name),

Enzyme Mechanism

Introduction

Thiosulphate is brought to the active center of the enzyme and stabilised by Arg109 and Arg119 because of their positively charged side chains. The Cys123 bound to heme acts as an electron relay for thiosulphate and propagates it down a chain of heme molecules within the heterodimer. This causes the thiosulphate to bond with Cys123. Another thiosulphate then enters the active site with the help of Ser127 and attacks the S-S bond made by the first thiosulphate and Cys123. This forms tetrathionate from the two thiosulphurs and regenerates the negative charge on the Cys123 sulphur atom.

Catalytic Residues Roles

UniProt PDB* (4v2k)
Cys123 Cys123(96)A Cys123 transfers electrons from thiosulphate to the adjacent heme irons, binds to thiosuphate and coordinates back to the Fe(III) heme atom after tetrathionate formation. electron pair donor, covalently attached, nucleofuge, electrophile
Ser127 Ser127(100)A Ser127 is responsible for guiding and stabilising the second thiosulphur molecule via hydrogen bonding of its OH group from its side chain. hydrogen bond donor, transition state stabiliser
Arg119, Arg109 Arg119(92)A, Arg109(82)A Electrostatic stabilisers that stabilise the negative charge of the thiosulphates. hydrogen bond donor, electrostatic stabiliser
*PDB label guide - RESx(y)B(C) - RES: Residue Name; x: Residue ID in PDB file; y: Residue ID in PDB sequence if different from PDB file; B: PDB Chain; C: Biological Assembly Chain if different from PDB. If label is "Not Found" it means this residue is not found in the reference PDB.

Chemical Components

electron relay, bimolecular nucleophilic addition, electron transfer, enzyme-substrate complex cleavage

References

  1. Grabarczyk DB et al. (2015), J Biol Chem, 290, 9209-9221. Mechanism of thiosulfate oxidation in the SoxA family of cysteine-ligated cytochromes. DOI:10.1074/jbc.M114.618025. PMID:25673696.
  2. Kurth JM et al. (2016), J Biol Chem, 291, 24804-24818. Electron Accepting Units of the Diheme Cytochrome c TsdA, a Bifunctional Thiosulfate Dehydrogenase/Tetrathionate Reductase. DOI:10.1074/jbc.M116.753863. PMID:27694441.
  3. Brito JA et al. (2015), J Biol Chem, 290, 9222-9238. Thiosulfate dehydrogenase (TsdA) from Allochromatium vinosum: structural and functional insights into thiosulfate oxidation. DOI:10.1074/jbc.M114.623397. PMID:25673691.
  4. Denkmann K et al. (2012), Environ Microbiol, 14, 2673-2688. Thiosulfate dehydrogenase: a widespread unusual acidophilic c-type cytochrome. DOI:10.1111/j.1462-2920.2012.02820.x. PMID:22779704.

Step 1. The thiosulphate is brought in and stabilised by Arg109 and Arg119 through their positively charged side chains. The negative sulphur from the thiosulphate donates its electrons to form a S-S bond between itself and the Cys123. The Cys123 relays the electrons it gained to the heme 1 iron reducing it to Fe(II) while forming a bond with thiosulphate.

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Catalytic Residues Roles

Residue Roles
Arg119(92)A electrostatic stabiliser, hydrogen bond donor
Arg109(82)A electrostatic stabiliser, hydrogen bond donor
Cys123(96)A electron pair donor, electrophile

Chemical Components

electron relay, ingold: bimolecular nucleophilic addition, electron transfer

Step 2. The iron atoms in the heme molecules are regenerated to Fe(III) by transferring electrons further down the enzyme.

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Catalytic Residues Roles

Residue Roles
Cys123(96)A covalently attached
Arg119(92)A electrostatic stabiliser
Arg109(82)A electrostatic stabiliser
Ser127(100)A hydrogen bond donor

Chemical Components

electron relay, electron transfer

Step 3. The second thiosulphate is brought in to react with the S-S bond between Cys123 and the first thiosulphate. This causes the two thiosulphates to form tetrathionate and Cys123 to become negatively charged and coordinate the iron atom of the same heme molecule again.

Download: Image, Marvin File

Catalytic Residues Roles

Residue Roles
Cys123(96)A nucleofuge
Arg119(92)A electrostatic stabiliser
Arg109(82)A electrostatic stabiliser
Ser127(100)A transition state stabiliser

Chemical Components

enzyme-substrate complex cleavage, ingold: bimolecular nucleophilic addition
Download: Image, Marvin File

Step 1. The thiosulphate is brought in and stabilised by Arg109 and Arg119 through their positively charged side chains. The negative sulphur from the thiosulphate donates its electrons to form a S-S bond between itself and the Cys123. The Cys123 relays the electrons it gained to the heme 1 iron reducing it to Fe(II) while forming a bond with thiosulphate.

Step 2. The iron atoms in the heme molecules are regenerated to Fe(III) by transferring electrons further down the enzyme.

Step 3. The second thiosulphate is brought in to react with the S-S bond between Cys123 and the first thiosulphate. This causes the two thiosulphates to form tetrathionate and Cys123 to become negatively charged and coordinate the iron atom of the same heme molecule again.

Products.

Contributors

Antonio Ribeiro, Marko Babić