Identification
Name:Cysteine desulfurase
Synonyms:
  • NifS protein homolog
  • ThiI transpersulfidase
Gene Name:iscS
Enzyme Class:
Biological Properties
General Function:Involved in metabolic process
Specific Function:Catalyzes the removal of elemental sulfur and selenium atoms from cysteine and selenocysteine to produce alanine. Functions as a sulfur delivery protein for NAD, biotin and Fe-S cluster synthesis. Transfers sulfur on 'Cys-456' of thiI in a transpersulfidation reaction. Transfers sulfur on 'Cys-19' of tusA in a transpersulfidation reaction. Functions also as a selenium delivery protein in the pathway for the biosynthesis of selenophosphate
Cellular Location:Cytoplasm (Probable)
SMPDB Pathways:
KEGG Pathways:
KEGG Reactions:
1.0[Enzyme]-cysteine+1.0Thumb1.0[Enzyme]-S-sulfanylcysteine+1.0Thumb
1.0[Enzyme]-cysteine + 1.0L-Cysteine ↔ 1.0[Enzyme]-S-sulfanylcysteine + 1.0L-Alanine
ReactionCard
SMPDB Reactions:
1.0Thumb+1.0an [L-cysteine desulfurase] L-cysteine persulfide1.0an [L-cysteine desulfurase] L-cysteine persulfide+1.0L-Alanine+1.0Thumb
1.0L-Cysteine + 1.0an [L-cysteine desulfurase] L-cysteine persulfide → 1.0an [L-cysteine desulfurase] L-cysteine persulfide + 1.0L-Alanine + 1.0L-Alanine
ReactionCard
Complex Reactions:
1.0IscS with bound sulfur+1.0MoaD Protein with bound AMP+1.0Thumb1.0Thumb+1.0IscS sulfur acceptor protein+1.0MoaD Protein with thiocarboxylate+1.0Thumb
1.0IscS with bound sulfur + 1.0MoaD Protein with bound AMP + 1.0NADH → 1.0Adenosine monophosphate + 1.0IscS sulfur acceptor protein + 1.0MoaD Protein with thiocarboxylate + 1.0NAD
ReactionCard
1.0[2Fe-1S] desulfurated iron-sulfur cluster+1.0IscS with bound sulfur+1.0IscU scaffold protein4.0Thumb+1.0IscS sulfur acceptor protein+1.0IscU with bound [2Fe-2S] cluster
1.0[2Fe-1S] desulfurated iron-sulfur cluster + 1.0IscS with bound sulfur + 1.0IscU scaffold protein → 4.0Hydrogen ion + 1.0IscS sulfur acceptor protein + 1.0IscU with bound [2Fe-2S] cluster
ReactionCard
1.0Thumb+1.0Thumb+1.0Thumb+1.0Thumb+1.0IscS with bound sulfur+1.0Thumb1.0Thumb+1.0Thumb+1.0Thumb+2.0Thumb+1.0IscS sulfur acceptor protein+1.0Thumb+1.0Thumb
1.0Adenosine triphosphate + 1.0Dehydroglycine + 1.01-Deoxy-D-xylulose 5-phosphate + 1.0Hydrogen ion + 1.0IscS with bound sulfur + 1.0NADPH → 1.04-Methyl-5-(2-phosphoethyl)-thiazole + 1.0Adenosine monophosphate + 1.0Carbon dioxide + 2.0Water + 1.0IscS sulfur acceptor protein + 1.0NADP + 1.0Pyrophosphate
ReactionCard
1.0Thumb+2.0Thumb+2.0IscS with bound sulfur+1.0IscU scaffold protein1.0Thumb+6.0Thumb+2.0IscS sulfur acceptor protein+1.0IscU with bound [2Fe-2S] cluster
1.0FADH2 + 2.0Iron + 2.0IscS with bound sulfur + 1.0IscU scaffold protein → 1.0FAD + 6.0Hydrogen ion + 2.0IscS sulfur acceptor protein + 1.0IscU with bound [2Fe-2S] cluster
ReactionCard
1.0Thumb+2.0Thumb+2.0IscS with bound sulfur+1.0IscU with bound [2Fe-2S] cluster1.0Thumb+6.0Thumb+2.0IscS sulfur acceptor protein+1.0IscU with two bound [2Fe-2S] clusters
1.0FADH2 + 2.0Iron + 2.0IscS with bound sulfur + 1.0IscU with bound [2Fe-2S] cluster → 1.0FAD + 6.0Hydrogen ion + 2.0IscS sulfur acceptor protein + 1.0IscU with two bound [2Fe-2S] clusters
ReactionCard
1.0Thumb+1.0IscS sulfur acceptor protein1.0Thumb+1.0IscS with bound sulfur
1.0L-Cysteine + 1.0IscS sulfur acceptor protein → 1.0L-Alanine + 1.0IscS with bound sulfur
ReactionCard
1.0Thumb+1.0acceptor1.0Thumb+1.0S-sulfanyl-acceptor
1.0L-Cysteine + 1.0acceptor → 1.0L-Alanine + 1.0S-sulfanyl-acceptor
ReactionCard
Metabolites:
ECMDB IDNameView
ECMDB012131-Deoxy-D-xylulose 5-phosphateMetaboCard
ECMDB200944-Methyl-5-(2-phosphoethyl)-thiazoleMetaboCard
ECMDB00045Adenosine monophosphateMetaboCard
ECMDB00538Adenosine triphosphateMetaboCard
ECMDB04030Carbon dioxideMetaboCard
ECMDB21328DehydroglycineMetaboCard
ECMDB01248FADMetaboCard
ECMDB01197FADH2MetaboCard
ECMDB21225Hydrogen ionMetaboCard
ECMDB00692IronMetaboCard
ECMDB00161L-AlanineMetaboCard
ECMDB00574L-CysteineMetaboCard
ECMDB00902NADMetaboCard
ECMDB01487NADHMetaboCard
ECMDB00217NADPMetaboCard
ECMDB04111NADPHMetaboCard
ECMDB04142PyrophosphateMetaboCard
ECMDB00494WaterMetaboCard
GO Classification:
Function
binding
catalytic activity
cofactor binding
cysteine desulfurase activity
pyridoxal phosphate binding
sulfurtransferase activity
transferase activity
transferase activity, transferring sulfur-containing groups
Process
cellular amino acid and derivative metabolic process
cellular amino acid metabolic process
cellular metabolic process
cysteine metabolic process
metabolic process
sulfur amino acid metabolic process
Gene Properties
Blattner:b2530
Gene OrientationCounterclockwise
Centisome Percentage:57.30
Left Sequence End2658339
Right Sequence End2659553
Gene Sequence:
>1215 bp
ATGAAAAATCCCTATTTCCCTACCGCACTTGGGTTGTATTTTAATTACCTGGTGCATGGT
ATGGGCGTCCTTTTGATGAGCCTGAATATGGCCTCGCTGGAGACACTTTGGCAGACTAAT
GCCGCGGGTGTCTCGATAGTTATCTCATCGCTGGGCATTGGTCGATTAAGTGTCTTGCTT
TTTGCAGGATTATTATCCGATCGCTTTGGTCGCCGCCCTTTTATCATGCTCGGGATGTGC
TGCTATATGGCCTTCTTTTTTGGCATCCTGCAGACCAATAACATCATTATCGCTTATGTT
TTTGGCTTTCTGGCGGGAATGGCAAACAGTTTTCTCGATGCAGGCACTTATCCCAGTTTG
ATGGAAGCTTTTCCACGCTCACCTGGGACAGCCAATATTTTAATTAAAGCATTTGTTTCC
AGCGGACAATTTTTATTACCGCTAATCATTAGCCTGTTAGTGTGGGCTGAACTGTGGTTC
GGTTGGTCCTTTATGATTGCTGCAGGCATTATGTTTATTAACGCTCTGTTTTTATACCGT
TGTACGTTCCCACCCCATCCGGGTCGTCGCTTACCTGTCATAAAGAAAACCACCAGCTCT
ACGGAACATCGCTGTTCAATTATCGATTTAGCCAGTTATACCTTATATGGCTATATCTCA
ATGGCAACGTTTTATCTGGTTAGCCAGTGGCTGGCACAGTACGGACAATTTGTTGCAGGC
ATGTCATACACTATGTCGATCAAACTACTCAGTATCTACACCGTGGGTTCGCTGCTTTGT
GTATTTATTACCGCTCCACTCATTCGTAATACCGTTCGCCCAACAACATTACTGATGCTG
TACACCTTTATCTCATTTATTGCTCTGTTTACCGTCTGCCTGCATCCCACATTTTATGTG
GTGATAATATTTGCTTTTGTCATTGGTTTTACCTCTGCTGGAGGTGTTGTGCAAATTGGC
CTGACGTTAATGGCTGAACGTTTCCCTTACGCTAAAGGTAAAGCTACAGGGATCTATTAC
AGTGCGGGCAGTATTGCGACCTTTACTATTCCGTTGATTACGGCTCATCTGTCCCAAAGA
AGTATTGCCGATATTATGTGGTTCGATACCGCCATCGCTGCCATCGGTTTTTTACTGGCA
CTGTTTATCGGCTTACGCAGCCGCAAAAAAACGCGGCATCACTCGCTAAAGGAAAATGTC
GCTCCGGGTGGGTAA
Protein Properties
Pfam Domain Function:
Protein Residues:404
Protein Molecular Weight:45089
Protein Theoretical pI:6
PDB File:1P3W
Signaling Regions:
  • None
Transmembrane Regions:
  • None
Protein Sequence:
>Cysteine desulfurase
MKLPIYLDYSATTPVDPRVAEKMMQFMTMDGTFGNPASRSHRFGWQAEEAVDIARNQIAD
LVGADPREIVFTSGATESDNLAIKGAANFYQKKGKHIITSKTEHKAVLDTCRQLEREGFE
VTYLAPQRNGIIDLKELEAAMRDDTILVSIMHVNNEIGVVQDIAAIGEMCRARGIIYHVD
ATQSVGKLPIDLSQLKVDLMSFSGHKIYGPKGIGALYVRRKPRVRIEAQMHGGGHERGMR
SGTLPVHQIVGMGEAYRIAKEEMATEMERLRGLRNRLWNGIKDIEEVYLNGDLEHGAPNI
LNVSFNYVEGESLIMALKDLAVSSGSACTSASLEPSYVLRALGLNDELAHSSIRFSLGRF
TTEEEIDYTIELVRKSIGRLRDLSPLWEMYKQGVDLNSIEWAHH
References
External Links:
ResourceLink
Uniprot ID:P0A6B7
Uniprot Name:ISCS_ECOLI
GenBank Gene ID:AP009048
Genebank Protein ID:85675078
PDB ID:1P3W
Ecogene ID:EG12677
Ecocyc:EG12677
ColiBase:b2530
Kegg Gene:b2530
EchoBASE ID:EB2542
CCDB:ISCS_ECOLI
BacMap:49176235
General Reference:
  • Blattner, F. R., Plunkett, G. 3rd, Bloch, C. A., Perna, N. T., Burland, V., Riley, M., Collado-Vides, J., Glasner, J. D., Rode, C. K., Mayhew, G. F., Gregor, J., Davis, N. W., Kirkpatrick, H. A., Goeden, M. A., Rose, D. J., Mau, B., Shao, Y. (1997). "The complete genome sequence of Escherichia coli K-12." Science 277:1453-1462. Pubmed: 9278503
  • Cupp-Vickery, J. R., Urbina, H., Vickery, L. E. (2003). "Crystal structure of IscS, a cysteine desulfurase from Escherichia coli." J Mol Biol 330:1049-1059. Pubmed: 12860127
  • Flint, D. H. (1996). "Escherichia coli contains a protein that is homologous in function and N-terminal sequence to the protein encoded by the nifS gene of Azotobacter vinelandii and that can participate in the synthesis of the Fe-S cluster of dihydroxy-acid dehydratase." J Biol Chem 271:16068-16074. Pubmed: 8663056
  • Hayashi, K., Morooka, N., Yamamoto, Y., Fujita, K., Isono, K., Choi, S., Ohtsubo, E., Baba, T., Wanner, B. L., Mori, H., Horiuchi, T. (2006). "Highly accurate genome sequences of Escherichia coli K-12 strains MG1655 and W3110." Mol Syst Biol 2:2006.0007. Pubmed: 16738553
  • Ikeuchi, Y., Shigi, N., Kato, J., Nishimura, A., Suzuki, T. (2006). "Mechanistic insights into sulfur relay by multiple sulfur mediators involved in thiouridine biosynthesis at tRNA wobble positions." Mol Cell 21:97-108. Pubmed: 16387657
  • Kambampati, R., Lauhon, C. T. (1999). "IscS is a sulfurtransferase for the in vitro biosynthesis of 4-thiouridine in Escherichia coli tRNA." Biochemistry 38:16561-16568. Pubmed: 10600118
  • Kiyasu, T., Asakura, A., Nagahashi, Y., Hoshino, T. (2000). "Contribution of cysteine desulfurase (NifS protein) to the biotin synthase reaction of Escherichia coli." J Bacteriol 182:2879-2885. Pubmed: 10781558
  • Lacourciere, G. M., Mihara, H., Kurihara, T., Esaki, N., Stadtman, T. C. (2000). "Escherichia coli NifS-like proteins provide selenium in the pathway for the biosynthesis of selenophosphate." J Biol Chem 275:23769-23773. Pubmed: 10829016
  • Lauhon, C. T., Kambampati, R. (2000). "The iscS gene in Escherichia coli is required for the biosynthesis of 4-thiouridine, thiamin, and NAD." J Biol Chem 275:20096-20103. Pubmed: 10781607
  • Link, A. J., Robison, K., Church, G. M. (1997). "Comparing the predicted and observed properties of proteins encoded in the genome of Escherichia coli K-12." Electrophoresis 18:1259-1313. Pubmed: 9298646
  • 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. Pubmed: 10739946
  • Schwartz, C. J., Djaman, O., Imlay, J. A., Kiley, P. J. (2000). "The cysteine desulfurase, IscS, has a major role in in vivo Fe-S cluster formation in Escherichia coli." Proc Natl Acad Sci U S A 97:9009-9014. Pubmed: 10908675
  • Takahashi, Y., Nakamura, M. (1999). "Functional assignment of the ORF2-iscS-iscU-iscA-hscB-hscA-fdx-ORF3 gene cluster involved in the assembly of Fe-S clusters in Escherichia coli." J Biochem 126:917-926. Pubmed: 10544286
  • Yamamoto, Y., Aiba, H., Baba, T., Hayashi, K., Inada, T., Isono, K., Itoh, T., Kimura, S., Kitagawa, M., Makino, K., Miki, T., Mitsuhashi, N., Mizobuchi, K., Mori, H., Nakade, S., Nakamura, Y., Nashimoto, H., Oshima, T., Oyama, S., Saito, N., Sampei, G., Satoh, Y., Sivasundaram, S., Tagami, H., Horiuchi, T., et, a. l. .. (1997). "Construction of a contiguous 874-kb sequence of the Escherichia coli -K12 genome corresponding to 50.0-68.8 min on the linkage map and analysis of its sequence features." DNA Res 4:91-113. Pubmed: 9205837