If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.
Locations of Mapped Genes:
|Superclasses:||Degradation/Utilization/Assimilation → Inorganic Nutrients Metabolism → Sulfur Compounds Metabolism → Sulfate Reduction|
Sulfur is an essential nutrient for all life forms. Plants, fungi, and many bacteria reduce inorganic sulfate to sulfide to cover their need for the element. Before the sulfur can be assimilated into biosynthetic pathways it needs to be reduced to hydrogen sulfide. Pathways catalyzing the reduction of sulfate to sulfide for the purpose of incorporation into newly synthesized molecules are called pathways of assimilatory sulfate reduction. In addition, certain organisms can use sulfate as an alternative electron acceptor in the absence of oxygen. Pathways of sulfate reduction for the purpose of energy production are called pathways of dissimilatory sulfate reduction.
The reduction of sulfate to sulfite requires two electrons at a standard redox potential (E0') of -516 mV, which is too high for physiological electron carriers [Thauer77]. The problem is solved by the activation of the sulfate, by forming a mixed anhydride between phosphate and sulfate as in adenosine 5'-phosphosulfate (APS) or 3'-phosphoadenylyl-sulfate (PAPS). This linkage lowers the potential to E0' = -60 mV, which is easily covered by thiols or pyrimidine nucleotides [Berndt04].
About This Pathway
In many bacteria and lower eukaryotes, assimilatory sulfate reduction proceeds via activation of sulfate to APS by the enzyme sulfate adenylyltransferase (also known as ATP sulfurylase). This enzyme has an unfavorable equilibrium (Keq ~ 10-7 M) in the direction of APS formation, and it has been postulated that the reaction is driven by the hydrolysis of PPi by a ubiquitous inorganic pyrophosphatase [Segel87]. In Escherichia coli K-12 it was found that the enzymes couples the formation of APS to hydrolysis of GTP [Liu94b].
Following sulfate activation, the pathway consists of phosphorylation of APS to PAPS, which is catalyzed by adenylylsulfate kinase (APS kinase), reduction to sulfite, which is catalyzed by the thioredoxin (or glutaredoxin)-dependent 3'-phospho-adenylylsulfate reductase (PAPS reductase), and a final reduction of sulfite to sulfide, catalyzed by a sulfite reductase.
Subpathways: sulfate activation for sulfonation
Berndt04: Berndt C, Lillig CH, Wollenberg M, Bill E, Mansilla MC, de Mendoza D, Seidler A, Schwenn JD (2004). "Characterization and reconstitution of a 4Fe-4S adenylyl sulfate/phosphoadenylyl sulfate reductase from Bacillus subtilis." J Biol Chem 279(9);7850-5. PMID: 14627706
Berendt95: Berendt U, Haverkamp T, Prior A, Schwenn JD (1995). "Reaction mechanism of thioredoxin: 3'-phospho-adenylylsulfate reductase investigated by site-directed mutagenesis." Eur J Biochem 1995;233(1);347-56. PMID: 7588765
Butland05: Butland G, Peregrin-Alvarez JM, Li J, Yang W, Yang X, Canadien V, Starostine A, Richards D, Beattie B, Krogan N, Davey M, Parkinson J, Greenblatt J, Emili A (2005). "Interaction network containing conserved and essential protein complexes in Escherichia coli." Nature 433(7025);531-7. PMID: 15690043
Chartron07: Chartron J, Shiau C, Stout CD, Carroll KS (2007). "3'-Phosphoadenosine-5'-phosphosulfate reductase in complex with thioredoxin: a structural snapshot in the catalytic cycle." Biochemistry 46(13);3942-51. PMID: 17352498
Christner81: Christner JA, Munck E, Janick PA, Siegel LM (1981). "Mossbauer spectroscopic studies of Escherichia coli sulfite reductase. Evidence for coupling between the siroheme and Fe4S4 cluster prosthetic groups." J Biol Chem 1981;256(5);2098-101. PMID: 6257697
Christner83: Christner JA, Munck E, Janick PA, Siegel LM (1983). "Mossbauer evidence for exchange-coupled siroheme and [4Fe-4S] prosthetic groups in Escherichia coli sulfite reductase. Studies of the reduced states and of a nitrite turnover complex." J Biol Chem 258(18);11147-56. PMID: 6309833
Coves93: Coves J, Niviere V, Eschenbrenner M, Fontecave M (1993). "NADPH-sulfite reductase from Escherichia coli. A flavin reductase participating in the generation of the free radical of ribonucleotide reductase." J Biol Chem 1993;268(25);18604-9. PMID: 8360156
Coves97: Coves J, Zeghouf M, Macherel D, Guigliarelli B, Asso M, Fontecave M (1997). "Flavin mononucleotide-binding domain of the flavoprotein component of the sulfite reductase from Escherichia coli." Biochemistry 1997;36(19);5921-8. PMID: 9153434
DiazMejia09: Diaz-Mejia JJ, Babu M, Emili A (2009). "Computational and experimental approaches to chart the Escherichia coli cell-envelope-associated proteome and interactome." FEMS Microbiol Rev 33(1);66-97. PMID: 19054114
Dyson90: Dyson HJ, Gippert GP, Case DA, Holmgren A, Wright PE (1990). "Three-dimensional solution structure of the reduced form of Escherichia coli thioredoxin determined by nuclear magnetic resonance spectroscopy." Biochemistry 1990;29(17);4129-36. PMID: 2193685
Eklund84: Eklund H, Cambillau C, Sjoberg BM, Holmgren A, Jornvall H, Hoog JO, Branden CI (1984). "Conformational and functional similarities between glutaredoxin and thioredoxins." EMBO J 1984;3(7);1443-9. PMID: 6378624
Eschenbrenner95: Eschenbrenner M, Coves J, Fontecave M (1995). "The flavin reductase activity of the flavoprotein component of sulfite reductase from Escherichia coli. A new model for the protein structure." J Biol Chem 1995;270(35);20550-5. PMID: 7657631
Eschenbrenner95a: Eschenbrenner M, Coves J, Fontecave M (1995). "NADPH-sulfite reductase flavoprotein from Escherichia coli: contribution to the flavin content and subunit interaction." FEBS Lett 1995;374(1);82-4. PMID: 7589518
Evrard99: Evrard A, Zeghouf M, Fontecave M, Roby C, Coves J (1999). "31P nuclear magnetic resonance study of the flavoprotein component of the Escherichia coli sulfite reductase." Eur J Biochem 261(2);430-7. PMID: 10215853
Faeder74: Faeder EJ, Davis PS, Siegel LM (1974). "Reduced nicotinamide adenine dinucleotide phosphate-sulfite reductase of enterobacteria. V. Studies with the Escherichia coli hemoflavoprotein depleted of flavin mononucleotide: distinct roles for the flavin adenine dinucleotide and flavin mononucleotide prosthetic groups in catalysis." J Biol Chem 1974;249(5);1599-609. PMID: 4150392
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