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discounted EARLY registration ends Dec 31, 2014
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12/28 - 12/31
for maintenance.
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discounted EARLY registration ends Dec 31, 2014
BioCyc websites MAYBE down
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for maintenance.
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discounted EARLY registration ends Dec 31, 2014
BioCyc websites MAYBE down
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Escherichia coli K-12 substr. MG1655 Enzyme: L-cysteine desulfurase

Gene: sufS Accession Numbers: G6906 (EcoCyc), b1680, ECK1676

Synonyms: csdB, ynhB

Regulation Summary Diagram: ?

Subunit composition of L-cysteine desulfurase = [SufS]2
         L-cysteine desulfurase = SufS

SufS is one of three members of the NifS protein family in E. coli [Patzer99]. The protein was initially thought to function mainly as a pyridoxal 5'-phosphate dependent selenocysteine lyase with high specificity for L-selenocysteine [Mihara99]. It was later determined that SufS functions as a cysteine desulfurase in a secondary pathway of iron-sulfur cluster assembly [Outten03]; the isc operon encodes the major assembly pathway [Takahashi02]. The Suf system appears to be responsible for Fe-S cluster synthesis when iron or sulfur metabolism is disrupted by iron starvation or oxidative stress [Outten04]. SufS-SufE is less susceptible to oxidative modification than IscS-IscU [Dai12].

As part of the cysteine desulfurase reaction, the conserved C364 residue of SufS is modified to a persulfide intermediate from which the sulfur can be transferred to Cys51 of SufE [Mihara00, OllagnierdeChou03]. The cysteine desulfurase activity of SufS is stimulated by SufE together with the SufB-SufC-SufD complex [Outten03]. SufE is both a cosubstrate of SufS, accepting sulfur at its C51 residue from the Cys364 persulfide of SufS, and an activator for the cysteine desulfurase activity of SufS. SufE binds near the active site of SufS and modulates the site's backbone dynamics [Singh13a]. The kinetic mechanism of sulfur transfer between SufS and SufE has been investigated, and a model for a protected sulfur transfer pathway of the Suf system has been proposed [Selbach13].

SufS facilitates the formation of the iron-sulfur cluster of ferredoxin in vitro, but does not interact with the IscU scaffold, which acts with IscS in iron-sulfur cluster assembly [Kurihara03]. Like CsdA and IscS, SufS can transfer sulfur from L-cysteine to activate MPT synthase in vitro. Of the three enzymes, CsdA is the most effective, while SufS shows the lowest activity [Leimkuhler01]. SufS does not play a major role in tRNA thionucleoside modification [Lauhon02, Mihara02].

Non-specific incorporation of selenium into proteins appears to occur via synthesis of free selenocysteine by the cysteine biosynthesis pathway [Muller97]. Free selenocysteine it is likely to be toxic to the cell; SufS may be responsible for its degradation [Turner98] and thereby also play a role in the provision of selenium to the selenophosphate synthesis protein SelD [Lacourciere00, Lacourciere02, Ogasawara05].

SufS crystal structures have been solved [Fujii00, Lima02, Mihara02a].

A C364A mutation at the predicted catalytic cysteine results in a severe defect in L-cysteine desulfurization, but a more mild defect in activity toward L-selenocysteine [Mihara00]. sufD, sufS or fhuF mutants exhibit a defect in utilization of ferrioxamine B as a source of iron [Patzer99]. A sufABCDSE deletion mutant grows normally, whereas a sufABCDSE isc double mutant exhibits synthetic lethality, indicating that these systems are redundant and that iron-sulfur cluster assembly is essential for viability. Overproduction of the sufABCDSE operon suppresses the growth defects of a Δisc strain [Takahashi02].

Expression of the suf operon is activated in response to oxidative stress by OxyR [Zheng01a] and IHF [Outten04] and is regulated in response to iron starvation by Fur [Patzer99, Outten04].

SufS: "sulfur"

Reviews: [Roche13, Py10, Fontecave05, Lacourciere01, Ellis01]

Citations: [Tokumoto04, Rojas05, Prabhakar05, Lee10, Bolstad10]

Locations: cytosol

Map Position: [1,757,327 <- 1,758,547] (37.88 centisomes)
Length: 1221 bp / 406 aa

Molecular Weight of Polypeptide: 44.434 kD (from nucleotide sequence), 43.0 kD (experimental) [Mihara99 ]

Molecular Weight of Multimer: 88.0 kD (experimental) [Mihara99]

Unification Links: ASAP:ABE-0005610 , DIP:DIP-9324N , EchoBASE:EB3720 , EcoGene:EG13962 , EcoliWiki:b1680 , EcoO157Cyc:Z2708 , ModBase:P77444 , OU-Microarray:b1680 , PortEco:sufS , Pride:P77444 , Protein Model Portal:P77444 , RefSeq:NP_416195 , RegulonDB:G6906 , SMR:P77444 , String:511145.b1680 , UniProt:P77444

Relationship Links: InterPro:IN-FAMILY:IPR000192 , InterPro:IN-FAMILY:IPR010970 , InterPro:IN-FAMILY:IPR015421 , InterPro:IN-FAMILY:IPR015422 , InterPro:IN-FAMILY:IPR015424 , InterPro:IN-FAMILY:IPR020578 , PDB:Structure:1C0N , PDB:Structure:1I29 , PDB:Structure:1JF9 , PDB:Structure:1KMJ , PDB:Structure:1KMK , Pfam:IN-FAMILY:PF00266 , Prosite:IN-FAMILY:PS00595

In Paralogous Gene Group: 428 (3 members)

In Reactions of unknown directionality:

Not in pathways:
an [L-cysteine desulfurase] + L-cysteine = an S-sulfanyl-[L-cysteine desulfurase] + L-alanine

Gene-Reaction Schematic: ?

Genetic Regulation Schematic: ?

GO Terms:

Biological Process: GO:0001887 - selenium compound metabolic process Inferred from experiment [Lacourciere00]
GO:0006790 - sulfur compound metabolic process Inferred from experiment [Dai12]
GO:0016226 - iron-sulfur cluster assembly Inferred from experiment [Kurihara03]
GO:0031162 - sulfur incorporation into metallo-sulfur cluster Inferred from experiment [OllagnierdeChou03]
GO:0006534 - cysteine metabolic process Inferred by computational analysis [GOA01a]
GO:0008152 - metabolic process Inferred by computational analysis [GOA01a]
Molecular Function: GO:0005515 - protein binding Inferred from experiment [Layer07, Outten03]
GO:0009000 - selenocysteine lyase activity Author statement Inferred from experiment Inferred by computational analysis [GOA06, GOA01, Mihara99]
GO:0030170 - pyridoxal phosphate binding Inferred from experiment Inferred by computational analysis [GOA01a, Mihara99]
GO:0031071 - cysteine desulfurase activity Inferred from experiment Inferred by computational analysis [GOA06, GOA01, GOA01a, Mihara99]
GO:0042803 - protein homodimerization activity Inferred from experiment [Mihara99]
GO:0003824 - catalytic activity Inferred by computational analysis [GOA01a]
GO:0016740 - transferase activity Inferred by computational analysis [UniProtGOA11a]
GO:0016829 - lyase activity Inferred by computational analysis [UniProtGOA11a]
Cellular Component: GO:0005737 - cytoplasm Inferred by computational analysis [UniProtGOA11, UniProtGOA11a, GOA06]
GO:0005829 - cytosol Inferred by computational analysis [DiazMejia09]

MultiFun Terms: metabolism metabolism of other compounds sulfur metabolism

Essentiality data for sufS knockouts: ?

Growth Medium Growth? T (°C) O2 pH Osm/L Growth Observations
LB enriched Yes 37 Aerobic 6.95   Yes [Gerdes03, Comment 1]
LB Lennox Yes 37 Aerobic 7   Yes [Baba06, Comment 2]
M9 medium with 1% glycerol Yes 37 Aerobic 7.2 0.35 Yes [Joyce06, Comment 3]
MOPS medium with 0.4% glucose Yes 37 Aerobic 7.2 0.22 Yes [Baba06, Comment 2]

Last-Curated ? 12-Nov-2013 by Keseler I , SRI International

Enzymatic reaction of: L-cysteine desulfurase

EC Number:

L-cysteine + an unsulfurated [sulfur carrier] <=> L-alanine + a sulfurated [sulfur carrier]

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

The reaction is physiologically favored in the direction shown.

In Pathways: superpathway of alanine biosynthesis , superpathway of thiamin diphosphate biosynthesis I , molybdenum cofactor biosynthesis , alanine biosynthesis III , thiazole biosynthesis I (E. coli)

Cofactors or Prosthetic Groups: pyridoxal 5'-phosphate [Mihara99]

Activators (Unknown Mechanism): sulfur acceptor for SufS cysteine desulfurase [Outten03]

Kinetic Parameters:

Specific Activity (U/mg)
an unsulfurated [sulfur carrier]

Enzymatic reaction of: cysteine sulfinate desulfinase (L-cysteine desulfurase)

EC Number: 3.13.1.-

3-sulfinoalanine + H2O <=> L-alanine + sulfite + H+

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction in which it was curated.

Reversibility of this reaction is unspecified.

Cofactors or Prosthetic Groups: pyridoxal 5'-phosphate [Mihara99]

Kinetic Parameters:

Km (μM)
Specific Activity (U/mg)

Enzymatic reaction of: selenocysteine lyase (L-cysteine desulfurase)

Synonyms: SCL, selenocysteine reductase, L-selenocysteine selenide-lyase (L-alanine-forming)

EC Number:

L-selenocysteine + a reduced electron acceptor <=> L-alanine + selenide + an oxidized electron acceptor + 2 H+

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

Reversibility of this reaction is unspecified.

Alternative Substrates for L-selenocysteine: L-cysteine [Mihara99 ]

Cofactors or Prosthetic Groups: pyridoxal 5'-phosphate [Comment 4, Mihara99]

Kinetic Parameters:

Specific Activity (U/mg)

Sequence Features

Feature Class Location Citations Comment
Mutagenesis-Variant 55
[Mihara02a, UniProt11]
Alternate sequence: H → A; UniProt: No effect.
Mutagenesis-Variant 123
[Mihara02a, UniProt11]
Alternate sequence: H → A; UniProt: Loss of function; possibly due to destabilization of PLP in the active site.
N6-pyridoxal-phosphate-Lys-Modification 226
[UniProt, 2011]
UniProt: N6-(pyridoxal phosphate)lysine.
Mutagenesis-Variant 364
[Mihara00, UniProt11]
Alternate sequence: C → A; UniProt: Abolishes activity towards L- cysteine but not towards selenocysteine.
Active-Site 364
UniProt: Cysteine persulfide intermediate;
Mutagenesis-Variant 379
[Mihara02a, UniProt11]
Alternate sequence: R → A; UniProt: Loss of function.

Gene Local Context (not to scale): ?

Transcription Unit:


Markus Krummenacker on Tue Oct 14, 1997:
Gene object created from Blattner lab Genbank (v. M52) entry.


Baba06: Baba T, Ara T, Hasegawa M, Takai Y, Okumura Y, Baba M, Datsenko KA, Tomita M, Wanner BL, Mori H (2006). "Construction of Escherichia coli K-12 in-frame, single-gene knockout mutants: the Keio collection." Mol Syst Biol 2;2006.0008. PMID: 16738554

Bolstad10: Bolstad HM, Wood MJ (2010). "An in vivo method for characterization of protein interactions within sulfur trafficking systems of E. coli." J Proteome Res 9(12);6740-51. PMID: 20936830

Dai12: Dai Y, Outten FW (2012). "The E. coli SufS-SufE sulfur transfer system is more resistant to oxidative stress than IscS-IscU." FEBS Lett 586(22);4016-22. PMID: 23068614

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

Ellis01: Ellis KE, Clough B, Saldanha JW, Wilson RJ (2001). "Nifs and Sufs in malaria." Mol Microbiol 41(5);973-81. PMID: 11555280

Fontecave05: Fontecave M, Choudens SO, Py B, Barras F (2005). "Mechanisms of iron-sulfur cluster assembly: the SUF machinery." J Biol Inorg Chem 10(7);713-21. PMID: 16211402

Fujii00: Fujii T, Maeda M, Mihara H, Kurihara T, Esaki N, Hata Y (2000). "Structure of a NifS homologue: X-ray structure analysis of CsdB, an Escherichia coli counterpart of mammalian selenocysteine lyase." Biochemistry 2000;39(6);1263-73. PMID: 10684605

Gerdes03: Gerdes SY, Scholle MD, Campbell JW, Balazsi G, Ravasz E, Daugherty MD, Somera AL, Kyrpides NC, Anderson I, Gelfand MS, Bhattacharya A, Kapatral V, D'Souza M, Baev MV, Grechkin Y, Mseeh F, Fonstein MY, Overbeek R, Barabasi AL, Oltvai ZN, Osterman AL (2003). "Experimental determination and system level analysis of essential genes in Escherichia coli MG1655." J Bacteriol 185(19);5673-84. PMID: 13129938

GOA01: GOA, MGI (2001). "Gene Ontology annotation based on Enzyme Commission mapping." Genomics 74;121-128.

GOA01a: GOA, DDB, FB, MGI, ZFIN (2001). "Gene Ontology annotation through association of InterPro records with GO terms."

GOA06: GOA, SIB (2006). "Electronic Gene Ontology annotations created by transferring manual GO annotations between orthologous microbial proteins."

Joyce06: Joyce AR, Reed JL, White A, Edwards R, Osterman A, Baba T, Mori H, Lesely SA, Palsson BO, Agarwalla S (2006). "Experimental and computational assessment of conditionally essential genes in Escherichia coli." J Bacteriol 188(23);8259-71. PMID: 17012394

Kurihara03: Kurihara T, Mihara H, Kato S, Yoshimura T, Esaki N (2003). "Assembly of iron-sulfur clusters mediated by cysteine desulfurases, IscS, CsdB and CSD, from Escherichia coli." Biochim Biophys Acta 1647(1-2);303-9. PMID: 12686149

Lacourciere00: Lacourciere GM, Mihara H, Kurihara T, Esaki N, Stadtman TC (2000). "Escherichia coli NifS-like proteins provide selenium in the pathway for the biosynthesis of selenophosphate." J Biol Chem 2000;275(31);23769-73. PMID: 10829016

Lacourciere01: Lacourciere GM, Stadtman TC (2001). "Utilization of selenocysteine as a source of selenium for selenophosphate biosynthesis." Biofactors 14(1-4);69-74. PMID: 11568442

Lacourciere02: Lacourciere GM (2002). "Selenium is mobilized in vivo from free selenocysteine and is incorporated specifically into formate dehydrogenase H and tRNA nucleosides." J Bacteriol 184(7);1940-6. PMID: 11889101

Lauhon02: Lauhon CT (2002). "Requirement for IscS in biosynthesis of all thionucleosides in Escherichia coli." J Bacteriol 184(24);6820-9. PMID: 12446632

Layer07: Layer G, Gaddam SA, Ayala-Castro CN, Ollagnier-de Choudens S, Lascoux D, Fontecave M, Outten FW (2007). "SufE transfers sulfur from SufS to SufB for iron-sulfur cluster assembly." J Biol Chem 282(18);13342-50. PMID: 17350958

Lee10: Lee J, Hiibel SR, Reardon KF, Wood TK (2010). "Identification of stress-related proteins in Escherichia coli using the pollutant cis-dichloroethylene." J Appl Microbiol 108(6);2088-102. PMID: 19919618

Leimkuhler01: Leimkuhler S, Rajagopalan KV (2001). "A sulfurtransferase is required in the transfer of cysteine sulfur in the in vitro synthesis of molybdopterin from precursor Z in Escherichia coli." J Biol Chem 276(25);22024-31. PMID: 11290749

Lima02: Lima CD (2002). "Analysis of the E. coli NifS CsdB protein at 2.0 A reveals the structural basis for perselenide and persulfide intermediate formation." J Mol Biol 315(5);1199-208. PMID: 11827487

Mihara00: Mihara H, Kurihara T, Yoshimura T, Esaki N (2000). "Kinetic and mutational studies of three NifS homologs from Escherichia coli: Mechanistic difference between L-cysteine desulfurase and L-selenocysteine lyase reactions." J. Biochem. 127:559-567 (2000). PMID: 10739946

Mihara02: Mihara H, Kato S, Lacourciere GM, Stadtman TC, Kennedy RA, Kurihara T, Tokumoto U, Takahashi Y, Esaki N (2002). "The iscS gene is essential for the biosynthesis of 2-selenouridine in tRNA and the selenocysteine-containing formate dehydrogenase H." Proc Natl Acad Sci U S A 99(10);6679-83. PMID: 11997471

Mihara02a: Mihara H, Fujii T, Kato S, Kurihara T, Hata Y, Esaki N (2002). "Structure of external aldimine of Escherichia coli CsdB, an IscS/NifS homolog: implications for its specificity toward selenocysteine." J Biochem (Tokyo) 131(5);679-85. PMID: 11983074

Mihara99: Mihara H, Maeda M, Fujii T, Kurihara T, Hata Y, Esaki N (1999). "A nifS-like gene, csdB, encodes an Escherichia coli counterpart of mammalian selenocysteine lyase. Gene cloning, purification, characterization and preliminary x-ray crystallographic studies." J Biol Chem 1999;274(21);14768-72. PMID: 10329673

Muller97: Muller S, Heider J, Bock A (1997). "The path of unspecific incorporation of selenium in Escherichia coli." Arch Microbiol 168(5);421-7. PMID: 9325431

Ogasawara05: Ogasawara Y, Lacourciere GM, Ishii K, Stadtman TC (2005). "Characterization of potential selenium-binding proteins in the selenophosphate synthetase system." Proc Natl Acad Sci U S A 102(4);1012-6. PMID: 15653770

OllagnierdeChou03: Ollagnier-de-Choudens S, Lascoux D, Loiseau L, Barras F, Forest E, Fontecave M (2003). "Mechanistic studies of the SufS-SufE cysteine desulfurase: evidence for sulfur transfer from SufS to SufE." FEBS Lett 555(2);263-7. PMID: 14644425

Outten03: Outten FW, Wood MJ, Munoz FM, Storz G (2003). "The SufE protein and the SufBCD complex enhance SufS cysteine desulfurase activity as part of a sulfur transfer pathway for Fe-S cluster assembly in E. coli." J Biol Chem 278(46):45713-9. PMID: 12941942

Outten04: Outten FW, Djaman O, Storz G (2004). "A suf operon requirement for Fe-S cluster assembly during iron starvation in Escherichia coli." Mol Microbiol 52(3);861-72. PMID: 15101990

Patzer99: Patzer SI, Hantke K (1999). "SufS is a NifS-like protein, and SufD is necessary for stability of the [2Fe-2S] FhuF protein in Escherichia coli." J Bacteriol 181(10);3307-9. PMID: 10322040

Prabhakar05: Prabhakar R, Morokuma K, Musaev DG (2005). "A comparative study of various computational approaches in calculating the structure of pyridoxal 5'-phosphate (PLP)-dependent beta-lyase protein. The importance of protein environment." J Comput Chem 26(5);443-6. PMID: 15688436

Py10: Py B, Barras F (2010). "Building Fe-S proteins: bacterial strategies." Nat Rev Microbiol 8(6);436-46. PMID: 20467446

Roche13: Roche B, Aussel L, Ezraty B, Mandin P, Py B, Barras F (2013). "Iron/sulfur proteins biogenesis in prokaryotes: formation, regulation and diversity." Biochim Biophys Acta 1827(3);455-69. PMID: 23298813

Rojas05: Rojas DM, Vasquez CC (2005). "Sensitivity to potassium tellurite of Escherichia coli cells deficient in CSD, CsdB and IscS cysteine desulfurases." Res Microbiol 156(4);465-71. PMID: 15862443

Selbach13: Selbach BP, Pradhan PK, Dos Santos PC (2013). "Protected sulfur transfer reactions by the Escherichia coli Suf system." Biochemistry 52(23);4089-96. PMID: 23672190

Singh13a: Singh H, Dai Y, Outten FW, Busenlehner LS (2013). "Escherichia coli SufE Sulfur Transfer Protein Modulates the SufS Cysteine Desulfurase through Allosteric Conformational Dynamics." J Biol Chem. PMID: 24196966

Takahashi02: Takahashi Y, Tokumoto U (2002). "A third bacterial system for the assembly of iron-sulfur clusters with homologs in archaea and plastids." J Biol Chem 277(32);28380-3. PMID: 12089140

Tokumoto04: Tokumoto U, Kitamura S, Fukuyama K, Takahashi Y (2004). "Interchangeability and distinct properties of bacterial Fe-S cluster assembly systems: functional replacement of the isc and suf operons in Escherichia coli with the nifSU-like operon from Helicobacter pylori." J Biochem (Tokyo) 136(2);199-209. PMID: 15496591

Turner98: Turner RJ, Weiner JH, Taylor DE (1998). "Selenium metabolism in Escherichia coli." Biometals 11(3);223-7. PMID: 9850565

UniProt, 2011: UniProt Consortium (2011). "UniProt version 2011-11 released on 2011-11-22 00:00:00." Database.

UniProt10: UniProt Consortium (2010). "UniProt version 2010-11 released on 2010-11-02 00:00:00." Database.

UniProt11: UniProt Consortium (2011). "UniProt version 2011-06 released on 2011-06-30 00:00:00." Database.

UniProtGOA11: UniProt-GOA (2011). "Gene Ontology annotation based on the manual assignment of UniProtKB Subcellular Location terms in UniProtKB/Swiss-Prot entries."

UniProtGOA11a: UniProt-GOA (2011). "Gene Ontology annotation based on manual assignment of UniProtKB keywords in UniProtKB/Swiss-Prot entries."

Zheng01a: Zheng M, Wang X, Templeton LJ, Smulski DR, LaRossa RA, Storz G (2001). "DNA microarray-mediated transcriptional profiling of the Escherichia coli response to hydrogen peroxide." J Bacteriol 183(15);4562-70. PMID: 11443091

Other References Related to Gene Regulation

Giel06: Giel JL, Rodionov D, Liu M, Blattner FR, Kiley PJ (2006). "IscR-dependent gene expression links iron-sulphur cluster assembly to the control of O-regulated genes in Escherichia coli." Mol Microbiol 60(4);1058-75. PMID: 16677314

Jang10: Jang S, Imlay JA (2010). "Hydrogen peroxide inactivates the Escherichia coli Isc iron-sulphur assembly system, and OxyR induces the Suf system to compensate." Mol Microbiol 78(6);1448-67. PMID: 21143317

Lee04b: Lee JH, Yeo WS, Roe JH (2004). "Induction of the sufA operon encoding Fe-S assembly proteins by superoxide generators and hydrogen peroxide: involvement of OxyR, IHF and an unidentified oxidant-responsive factor." Mol Microbiol 51(6);1745-55. PMID: 15009899

Partridge09: Partridge JD, Bodenmiller DM, Humphrys MS, Spiro S (2009). "NsrR targets in the Escherichia coli genome: new insights into DNA sequence requirements for binding and a role for NsrR in the regulation of motility." Mol Microbiol 73(4);680-94. PMID: 19656291

Yeo06: Yeo WS, Lee JH, Lee KC, Roe JH (2006). "IscR acts as an activator in response to oxidative stress for the suf operon encoding Fe-S assembly proteins." Mol Microbiol 61(1);206-18. PMID: 16824106

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Please cite the following article in publications resulting from the use of EcoCyc: Nucleic Acids Research 41:D605-12 2013
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