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MetaCyc Enzyme: Sox enzyme system

Synonyms: thiosulfate-oxidizing multi-enzyme system, TOMES

Species: Paracoccus pantotrophus

Subunit composition of Sox enzyme system = [(SoxX)(SoxA)][SoxB][([SoxC][SoxD])2][(SoxY)(SoxZ)]
         SoxXA = (SoxX)(SoxA) (extended summary available)
         (SoxCD)2 = ([SoxC][SoxD])2 (summary available)
                 SoxCD = (SoxC)(SoxD)
         SoxYZ = (SoxY)(SoxZ) (extended summary available)

Summary:
Paracoccus pantotrophus posseses a periplasmic enzyme complex known as the Sox enzyme system (for sulfur oxidation) that is able to oxidize thiosulfate to sulfate with no intermediates [Friedrich00].

The genes, soxXYZABCD, part of the sox gene cluster, encode 4 proteins which can be combined in vitro to reconstitute an active Sox enzyme complex. The four proteins encoded by these seven genes are SoxXA, SoxYZ, SoxB, and SoxCD. SoxXA is a heterodimeric c-type cytochrome; SoxYZ is a heterodimeric protein that binds thiosulfate covalently. SoxB is a monomer that contains two manganese atoms [Wodara97]. SoxCD is an α2β2 heterotetramer composed of two units each of SoxC, a molybdenum cofactor-containing subunit, and SoxD, a diheme c-type cytochrome [Quentmeier00].

An in vitro reconstituted Sox system mediates not only thiosulfate, but also sulfite-, S0-, and hydrogen sulfide-dependent cytochrome c reduction [Wodara97, Rother01]. Sulfite oxidation occurs as described in the following equation, and results in the transfer of only 2 electrons per mol substrate:

sulfite + H2O = sulfate + 2e- + 2H+

In addition, sulfite oxidation does not require the presence of the SoxCD protein.

Based on these results, a model has been proposed for the mechanism of the Sox system [Friedrich01]. According to this model, the first step is the SoxXA-mediated binding of thiosulfate or sulfite to a cysteine residue of SoxY. When thiosulfate binds, the resulting SoxY-thiocysteine-S-sulfate is then hydrolyzed by SoxB, liberating a sulfate, and forming a SoxY-S-thiocysteine. SoxCD would then successively oxidize the outer sulfur atom, using three water molecules and forming SoxY-cyteine-S-sulfate. Finally, the second sulfate group is hydrolyzed by SoxB, bringing the cysteine residue of SoxY to its initial condition.

Locations: periplasmic space

Gene-Reaction Schematic: ?

GO Terms:

Cellular Component: GO:0030288 - outer membrane-bounded periplasmic space [Friedrich00]

Credits:
Created 10-Aug-1999 by Pellegrini-Toole A , Marine Biological Laboratory
Revised 31-Aug-2006 by Caspi R , SRI International


Enzymatic reaction of: Sox enzyme system

2 sulfate[in] + 11 H+[in] + 8 e- <=> thiosulfate[in] + 5 H2O[in]

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction of enzyme catalysis.

This reaction is reversible.


Component enzyme of Sox enzyme system : SoxXA

Locations: periplasmic space

Molecular Weight: 45 kD (experimental) [Dambe05]

GO Terms:

Cellular Component: GO:0030288 - outer membrane-bounded periplasmic space [Friedrich00]

Catalyzes:
a [SoxY protein]-L-cysteine + thiosulfate + 2 an oxidized c-type cytochrome → a [SoxY protein]-thiocysteine-S-sulfate + 2 a reduced c-type cytochrome + 2 H+

Summary:
SoxXA is a heterodimeric c-type cytochrome which is a part of the Sox enzyme system of Paracoccus pantotrophus. It is composed of the 16 kDa monoheme subunit SoxX and the 29 kDa diheme subunit SoxA [Friedrich00, Rother02]. The hemes of SoxA are designated heme1 and heme2, and the heme group of SoxX is designated heme3 [Bamford02, Cheesman01]. In in vitro assays performed with reconstructed Sox enzyme system, SoxXA is believed to deliver two electrons per molecule of thiosulfate to horse heart cytochrome c [Rother01, Bardischewsky05].

Closely related SoxXA cytochrome complexes have been identified from other chemotrophic [Kappler04, Mukhopadhyaya00] and phototrophic bacteria [AppiaAyme01, Hard92]. Most SoxA proteins isolated from other organisms are also diheme cytochromes. An exception is SoxA of Starkeya novella which does not contain a heme1 [Kappler04]. As SoxXA from Starkeya novella has an identical function to the Paracoccus pantotrophus protein, it is likely that heme1 does not play a significant role in sulfur oxidation [Dambe05].


Subunit of SoxXA: SoxX

Gene: soxX Accession Number: G-9551 (MetaCyc)

Locations: periplasmic space

Molecular Weight: 16.422 kD (from nucleotide sequence)

GO Terms:

Cellular Component: GO:0030288 - outer membrane-bounded periplasmic space [Friedrich00]

Unification Links: Protein Model Portal:Q9LCV0 , SMR:Q9LCV0 , UniProt:Q9LCV0

Relationship Links: InterPro:IN-FAMILY:IPR003088 , InterPro:IN-FAMILY:IPR009056 , PDB:Structure:2C1D , Pfam:IN-FAMILY:PF00034 , Prosite:IN-FAMILY:PS51007

Summary:
SoxX, a 16 kDa monoheme protein, is a subunit of SoxXA, a heterodimeric c-type cytochrome which is a part of the Sox enzyme system of Paracoccus pantotrophus [Friedrich00, Rother02].

The heme group of SoxX is designated heme3 [Bamford02, Cheesman01]. In in vitro assays performed with reconstructed Sox enzyme system, SoxXA is believed to deliver two electrons per molecule of thiosulfate to horse heart cytochrome c [Rother01, Bardischewsky05].


Subunit of SoxXA: SoxA

Synonyms: cytochrome c subunit

Gene: soxA Accession Number: G-309 (MetaCyc)

Locations: periplasmic space

Molecular Weight: 31.748 kD (from nucleotide sequence)

Molecular Weight: 30.452 kD (experimental) [Friedrich98]

GO Terms:

Cellular Component: GO:0030288 - outer membrane-bounded periplasmic space [Friedrich00]

Unification Links: Protein Model Portal:O33434 , SMR:O33434 , UniProt:O33434

Relationship Links: InterPro:IN-FAMILY:IPR009056 , InterPro:IN-FAMILY:IPR011031 , InterPro:IN-FAMILY:IPR025710 , PDB:Structure:2C1D , Prosite:IN-FAMILY:PS51007 , Prosite:IN-FAMILY:PS51008

Summary:
SoxA, a 16 kDa monoheme protein, is a subunit of SoxXA, a heterodimeric c-type cytochrome which is a part of the Sox enzyme system of Paracoccus pantotrophus [Friedrich00, Rother02].

The hemes of SoxA are designated heme1 and heme2 [Bamford02, Cheesman01]. In in vitro assays performed with reconstructed Sox enzyme system, SoxXA is believed to deliver two electrons per molecule of thiosulfate to horse heart cytochrome c [Rother01, Bardischewsky05].

Closely related SoxXA cytochrome complexes have been identified from other chemotrophic [Kappler04, Mukhopadhyaya00] and phototrophic bacteria [AppiaAyme01, Hard92]. Most SoxA proteins isolated from other organisms are also diheme cytochromes. An exception is SoxA of Starkeya novella which does not contain a heme1 [Kappler04]. As SoxXA from Starkeya novella has an identical function to the Paracoccus pantotrophus protein, it is likely that heme1 does not play a significant role in sulfur oxidation [Dambe05].


Component enzyme of Sox enzyme system : SoxB

Synonyms: thiosulfate hydrolase, sulfatase, sulfate thiol esterase

Gene: soxB Accession Number: G-308 (MetaCyc)

Locations: periplasmic space

Molecular Weight: 58.611 kD (from nucleotide sequence)

GO Terms:

Cellular Component: GO:0030288 - outer membrane-bounded periplasmic space [Friedrich00]

Unification Links: Protein Model Portal:P72177 , UniProt:P72177

Relationship Links: InterPro:IN-FAMILY:IPR006179 , InterPro:IN-FAMILY:IPR006311 , InterPro:IN-FAMILY:IPR008334 , Panther:IN-FAMILY:PTHR11575 , Pfam:IN-FAMILY:PF02872 , Prints:IN-FAMILY:PR01607 , Prosite:IN-FAMILY:PS51318

Catalyzes:
a [SoxY protein]-L-cysteine-S-sulfate + H2O → a [SoxY protein]-L-cysteine + sulfate + H+ ,
a [SoxY protein]-thiocysteine-S-sulfate + H2O → a [SoxY protein]-S-thiocysteine + sulfate + H+

Summary:
SoxB is a di-manganese monomeric protein which is a part of the Sox enzyme system of Paracoccus pantotrophus. The protein was proposed to function as a sulfide dehydrogenase [Schneider94, Wodara94], but that assignment seems to be questionable [Friedrich98]. Instead, the role of SoxB is now believed to be the hydrolysis of the sulfonate moiety of both the SoxY-cysteine-thiosulfonate complex formed by the action of the SoxXA protein, yielding SoxY-cysteine persulfide, and the SoxY-cysteine-S-sulfate, restoring the cysteine residue of SoxY to its normal condition [Quentmeier01, Friedrich01].

The monomeric SoxB protein contains two manganese atoms and a pyroglutamate (cycloglutamate) as N-terminus. Its predicted molecular mass of 58,611Da is identical to that determined by electrospray mass spectrometry [Quentmeier03]. A multifrequency EPR analysis of the dimanganese cluster of SoxB has been performed [Epel05].


Component enzyme of Sox enzyme system : (SoxCD)2

Locations: periplasmic space

Molecular Weight: 180 kD (experimental) [Bardischewsky05]

GO Terms:

Cellular Component: GO:0030288 - outer membrane-bounded periplasmic space [Friedrich00]

Catalyzes:
a [SoxY protein]-S-thiocysteine + 6 an oxidized c-type cytochrome + 3 H2O → a [SoxY protein]-L-cysteine-S-sulfate + 6 a reduced c-type cytochrome + 7 H+

Summary:
Sulfur dehydrogenase, (SoxCD)2, is an essential part of the Sox enzyme system of the chemotrophic bacterium Paracoccus pantotrophus. (SoxCD)2 is an α2β2 complex composed of the molybdoprotein SoxC and the hybrid diheme c-type cytochrome SoxD

(SoxCD)2 is proposed to successively oxidize the outer sulfur atom bound to SoxY-S-thiocysteine, using three water molecules and forming SoxY-cyteine-S-sulfate. During the process, six-electrons are transferred to a cytochreome c [Bardischewsky05, Friedrich01].


Subunit of (SoxCD)2: SoxCD

Locations: periplasmic space

GO Terms:

Cellular Component: GO:0030288 - outer membrane-bounded periplasmic space [Friedrich00]


Subunit of SoxCD: SoxC

Synonyms: sulfur dehydrogenase

Gene: soxC Accession Number: G-307 (MetaCyc)

Locations: periplasmic space

Molecular Weight: 47.339 kD (from nucleotide sequence)

Molecular Weight: 43.442 kD (experimental) [Bardischewsky05]

GO Terms:

Cellular Component: GO:0030288 - outer membrane-bounded periplasmic space [Friedrich00]

Summary:
SoxC is one of the subunits of (SoxCD)2, an essential part of the Sox enzyme system of the chemotrophic bacterium Paracoccus pantotrophus.

The soxC gene encodes a 430-amino-acid polypeptide that includes a signal peptide of 40 amino acids with a RR motif present in periplasmic proteins. The mature soxC gene product exhibits high amino acid sequence similarity to the eukaryotic molybdoenzyme sulfite oxidase and to nitrate reductase [Wodara97].

(SoxCD)2 is proposed to successively oxidize the outer sulfur atom bound to SoxY-S-thiocysteine using three water molecules and forming SoxY-cyteine-S-sulfate. During the process, six-electrons are transferred to a cytochreome c [Bardischewsky05, Friedrich01].


Subunit of SoxCD: SoxD

Synonyms: cytochrome c

Gene: soxD Accession Number: G-306 (MetaCyc)

Locations: periplasmic space

Molecular Weight: 39.983 kD (from nucleotide sequence) [Wodara97]

Molecular Weight: 37.637 kD (experimental) [Bardischewsky05]

GO Terms:

Cellular Component: GO:0030288 - outer membrane-bounded periplasmic space [Friedrich00]

Summary:
SoxD of Paracoccus pantotrophus is a periplasmic hybrid cytochrome of 384 amino acids with two heme domains. Both heme domains are linked by a proline-alanine-rich intervening sequence of about 35 amino acids [Wodara97]. SoxD is one of the subunits of (SoxCD)2, an essential part of the Sox enzyme system of the chemotrophic bacterium Paracoccus pantotrophus.

Amino acid sequence analysis identified the heme-1 domain of SoxD proteins to be specific for sulfur dehydrogenases and to contain a novel ProCysMetXaaAspCys motif. The heme-2 domain is related to various cytochromes c2[Bardischewsky05]

The heme-1 domain is crucial for catalytic activity, electron yield, and transfer of the electrons to the cytoplasmic membrane, while the heme-2 domain mediates the tetrameric structure of sulfur dehydrogenase [Bardischewsky05].


Subunit of Sox enzyme system: SoxYZ

Synonyms: thiosulfate binding complex

Locations: periplasmic space

Molecular Weight: 29 kD (experimental) [Friedrich00]

GO Terms:

Cellular Component: GO:0030288 - outer membrane-bounded periplasmic space [Friedrich00]

Summary:
SoxY is a sulfur covalently-binding protein, which binds sulfur anions, including sulfur, sulfite, thiosulfate and sulfate, to form a SoxY-thiocysteine-S-sulfur compound adducts [Quentmeier01]. SoxZ is a sulfur compound chelating protein.

SoxY and SoxZ combine with each other to form the SoxYZ complex. A thiosulfate ion then combines with the free thiol group of a conserved cysteine residue (Cys138) of SoxY to form SoxY-thiocysteine-S-thiosulfate, the first covalently bound sulfur adduct in the sulfur oxidation pathway of Paracoccus pantotrophus [Quentmeier03].

The residues of SoxY, SoxZ, and SoxB involved in the interactions among them have been identified [Bagchi05].

In native gradient polyacrylamide gels SoxYZ sometimes appears as a 50-kDa α2β2 heterotetramer [Friedrich00]. Neither SoxY nor SoxZ contains a cofactor or metal.


Subunit of SoxYZ: SoxY

Gene: soxY Accession Number: G-9550 (MetaCyc)

Locations: periplasmic space

Molecular Weight: 13.831 kD (from nucleotide sequence)

Molecular Weight: 16.0 kD (experimental) [Friedrich98]

GO Terms:

Cellular Component: GO:0030288 - outer membrane-bounded periplasmic space [Friedrich00]

Unification Links: Protein Model Portal:Q9LCU9 , SMR:Q9LCU9 , UniProt:Q9LCU9

Relationship Links: InterPro:IN-FAMILY:IPR016568 , PDB:Structure:2OX5 , PDB:Structure:2OXG , PDB:Structure:2OXH

Summary:
SoxY is a sulfur covalently-binding protein, which binds sulfur anions, including sulfur, sulfite, thiosulfate and sulfate, to form a SoxY-thiocysteine-S-sulfur compound adducts [Quentmeier01]. When SoxY bind thiosulfate, it forms SoxY-thiocysteine-S-sulfate, the first covalently bound sulfur adduct in the sulfur oxidation pathway of Paracoccus pantotrophus.

SoxY and SoxZ combine with each other to form the SoxYZ complex. The sulfate ion then combines with the free thiol group of a conserved cysteine residue (Cys138) of SoxY to form SoxY-thiocysteine-S-sulfate [Quentmeier03].


Subunit of SoxYZ: SoxZ

Gene: soxZ Accession Number: G-9549 (MetaCyc)

Locations: periplasmic space

Molecular Weight: 11.85 kD (from nucleotide sequence)

Molecular Weight: 12.0 kD (experimental) [Friedrich98]

GO Terms:

Cellular Component: GO:0030288 - outer membrane-bounded periplasmic space [Friedrich00]

Unification Links: Protein Model Portal:Q9LCU8 , SMR:Q9LCU8 , UniProt:Q9LCU8

Relationship Links: InterPro:IN-FAMILY:IPR013783 , InterPro:IN-FAMILY:IPR014756 , InterPro:IN-FAMILY:IPR014880 , PDB:Structure:2OX5 , PDB:Structure:2OXG , PDB:Structure:2OXH , Pfam:IN-FAMILY:PF08770

Summary:
SoxZ is a sulfur compound chelating protein.

SoxZ combines with SoxY to form the SoxYZ complex. The sulfate ion then combines with the free thiol group of a conserved cysteine residue (Cys138) of SoxY to form SoxY-thiocysteine-S-sulfate [Quentmeier03].


References

AppiaAyme01: Appia-Ayme C, Little PJ, Matsumoto Y, Leech AP, Berks BC (2001). "Cytochrome complex essential for photosynthetic oxidation of both thiosulfate and sulfide in Rhodovulum sulfidophilum." J Bacteriol 183(20);6107-18. PMID: 11567011

Bagchi05: Bagchi A, Ghosh TC (2005). "A structural study towards the understanding of the interactions of SoxY, SoxZ, and SoxB, leading to the oxidation of sulfur anions via the novel global sulfur oxidizing (sox) operon." Biochem Biophys Res Commun 335(2);609-15. PMID: 16084835

Bamford02: Bamford VA, Bruno S, Rasmussen T, Appia-Ayme C, Cheesman MR, Berks BC, Hemmings AM (2002). "Structural basis for the oxidation of thiosulfate by a sulfur cycle enzyme." EMBO J 21(21);5599-610. PMID: 12411478

Bardischewsky05: Bardischewsky F, Quentmeier A, Rother D, Hellwig P, Kostka S, Friedrich CG (2005). "Sulfur dehydrogenase of Paracoccus pantotrophus: the heme-2 domain of the molybdoprotein cytochrome c complex is dispensable for catalytic activity." Biochemistry 44(18);7024-34. PMID: 15865447

Cheesman01: Cheesman MR, Little PJ, Berks BC (2001). "Novel heme ligation in a c-type cytochrome involved in thiosulfate oxidation: EPR and MCD of SoxAX from Rhodovulum sulfidophilum." Biochemistry 40(35);10562-9. PMID: 11523998

Dambe05: Dambe T, Quentmeier A, Rother D, Friedrich C, Scheidig AJ (2005). "Structure of the cytochrome complex SoxXA of Paracoccus pantotrophus, a heme enzyme initiating chemotrophic sulfur oxidation." J Struct Biol 152(3);229-34. PMID: 16297640

Epel05: Epel B, Schafer KO, Quentmeier A, Friedrich C, Lubitz W (2005). "Multifrequency EPR analysis of the dimanganese cluster of the putative sulfate thiohydrolase SoxB of Paracoccus pantotrophus." J Biol Inorg Chem 10(6);636-42. PMID: 16133204

Franz07: Franz B, Lichtenberg H, Hormes J, Modrow H, Dahl C, Prange A (2007). "Utilization of solid "elemental" sulfur by the phototrophic purple sulfur bacterium Allochromatium vinosum: a sulfur K-edge X-ray absorption spectroscopy study." Microbiology 153(Pt 4);1268-74. PMID: 17379736

Friedrich00: Friedrich CG, Quentmeier A, Bardischewsky F, Rother D, Kraft R, Kostka S, Prinz H (2000). "Novel genes coding for lithotrophic sulfur oxidation of Paracoccus pantotrophus GB17." J Bacteriol 182(17);4677-87. PMID: 10940005

Friedrich01: Friedrich CG, Rother D, Bardischewsky F, Quentmeier A, Fischer J (2001). "Oxidation of reduced inorganic sulfur compounds by bacteria: emergence of a common mechanism?." Appl Environ Microbiol 67(7);2873-82. PMID: 11425697

Friedrich98: Friedrich CG (1998). "Physiology and genetics of sulfur-oxidizing bacteria." Adv Microb Physiol 1998;39;235-89. PMID: 9328649

Hard92: Hard K, Van Zadelhoff G, Moonen P, Kamerling JP, Vliegenthart FG (1992). "The Asn-linked carbohydrate chains of human Tamm-Horsfall glycoprotein of one male. Novel sulfated and novel N-acetylgalactosamine-containing N-linked carbohydrate chains." Eur J Biochem 209(3);895-915. PMID: 1425697

Kappler04: Kappler U, Aguey-Zinsou KF, Hanson GR, Bernhardt PV, McEwan AG (2004). "Cytochrome c551 from Starkeya novella: characterization, spectroscopic properties, and phylogeny of a diheme protein of the SoxAX family." J Biol Chem 279(8);6252-60. PMID: 14645228

Mukhopadhyaya00: Mukhopadhyaya PN, Deb C, Lahiri C, Roy P (2000). "A soxA gene, encoding a diheme cytochrome c, and a sox locus, essential for sulfur oxidation in a new sulfur lithotrophic bacterium." J Bacteriol 182(15);4278-87. PMID: 10894738

Quentmeier00: Quentmeier A, Kraft R, Kostka S, Klockenkamper R, Friedrich CG (2000). "Characterization of a new type of sulfite dehydrogenase from Paracoccus pantotrophus GB17." Arch Microbiol 173(2);117-25. PMID: 10795683

Quentmeier01: Quentmeier A, Friedrich CG (2001). "The cysteine residue of the SoxY protein as the active site of protein-bound sulfur oxidation of Paracoccus pantotrophus GB17." FEBS Lett 503(2-3);168-72. PMID: 11513876

Quentmeier03: Quentmeier A, Hellwig P, Bardischewsky F, Grelle G, Kraft R, Friedrich CG (2003). "Sulfur oxidation in Paracoccus pantotrophus: interaction of the sulfur-binding protein SoxYZ with the dimanganese SoxB protein." Biochem Biophys Res Commun 312(4);1011-8. PMID: 14651972

Rother01: Rother D, Henrich HJ, Quentmeier A, Bardischewsky F, Friedrich CG (2001). "Novel genes of the sox gene cluster, mutagenesis of the flavoprotein SoxF, and evidence for a general sulfur-oxidizing system in Paracoccus pantotrophus GB17." J Bacteriol 183(15);4499-508. PMID: 11443084

Rother02: Rother D, Friedrich CG (2002). "The cytochrome complex SoxXA of Paracoccus pantotrophus is produced in Escherichia coli and functional in the reconstituted sulfur-oxidizing enzyme system." Biochim Biophys Acta 1598(1-2);65-73. PMID: 12147345

Schneider94: Schneider A, Friedrich C (1994). "Sulfide dehydrogenase is identical with the SoxB protein of the thiosulfate-oxidizing enzyme system of Paracoccus denitrificans GB17." FEBS Lett 350(1);61-5. PMID: 8062925

Steudel00: Steudel, R. (2000). "The chemical sulfur cycle." Environmental Technologies to Treat Sulfur Pollution, pp. 1-31. Edited by P. N. L. Lens & L. Hulshof Pol. London: IWA Publishing.

Wodara94: Wodara C, Kostka S, Egert M, Kelly DP, Friedrich CG (1994). "Identification and sequence analysis of the soxB gene essential for sulfur oxidation of Paracoccus denitrificans GB17." J Bacteriol 1994;176(20);6188-91. PMID: 7928987

Wodara97: Wodara C, Bardischewsky F, Friedrich CG (1997). "Cloning and characterization of sulfite dehydrogenase, two c-type cytochromes, and a flavoprotein of Paracoccus denitrificans GB17: essential role of sulfite dehydrogenase in lithotrophic sulfur oxidation." J Bacteriol 1997;179(16);5014-23. PMID: 9260941


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Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
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