DB code: D00659

CATH domain 3.90.1150.10 : Aspartate Aminotransferase, domain 1 Catalytic domain
3.40.640.10 : Aspartate Aminotransferase; domain 2 Catalytic domain
E.C. 2.8.1.7
CSA 1ecx
M-CSA 1ecx
MACiE

CATH domain Related DB codes (homologues)

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
P0A6B7 Cysteine desulfurase
EC 2.8.1.7
NifS protein homolog
ThiI transpersulfidase
YP_026169.1 (Protein)
NC_000913.2 (DNA/RNA sequence)
YP_490758.1 (Protein)
NC_007779.1 (DNA/RNA sequence)
PF00266 (Aminotran_5)
[Graphical View]
P0A6B9 Cysteine desulfurase
EC 2.8.1.7
NP_289087.1 (Protein)
NC_002655.2 (DNA/RNA sequence)
NP_311423.2 (Protein)
NC_002695.1 (DNA/RNA sequence)
PF00266 (Aminotran_5)
[Graphical View]
Q9X218
Aminotransferase, class V
Cysteine desulfurase
EC 2.8.1.7
NP_229492.1 (Protein)
NC_000853.1 (DNA/RNA sequence)
PF00266 (Aminotran_5)
[Graphical View]
Q55793 Probable cysteine desulfurase
EC 2.8.1.7
NP_442475.1 (Protein)
NC_000911.1 (DNA/RNA sequence)
YP_005652536.1 (Protein)
NC_017277.1 (DNA/RNA sequence)
YP_007452351.1 (Protein)
NC_020286.1 (DNA/RNA sequence)
PF00266 (Aminotran_5)
[Graphical View]

KEGG enzyme name
Cysteine desulfurase
IscS
NIFS
NifS
SufS
Cysteine desulfurylase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P0A6B7 ISCS_ECOLI L-cysteine + acceptor = L-alanine + S-sulfanyl-acceptor. Homodimer. The homodimer interacts with tusA. Cytoplasm (Probable). Pyridoxal phosphate.
P0A6B9 ISCS_ECO57 L-cysteine + acceptor = L-alanine + S-sulfanyl-acceptor Pyridoxal phosphate.
Q9X218 Q9X218_THEMA Pyridoxal phosphate.
Q55793 CSD_SYNY3 L-cysteine + acceptor = L-alanine + S-sulfanyl-acceptor. Pyridoxal phosphate.

KEGG Pathways
Map code Pathways E.C.
MAP00730 Thiamine metabolism

Compound table
Cofactors Substrates Products Intermediates
KEGG-id C00018 C00097 L00106 C00041 L00105 I00165 I00166 I00167 I00171 C15812 I00030 I00032 I00049
E.C.
Compound Pyridoxal phosphate L-cysteine Acceptor for sulfur L-alanine S-sulfanyl-acceptor External aldimine intermediate (PLP-L-Cys) Quinonoid intermediate (PLP-Cys) Ketimine intermediate (PLP-Cys) Aminoacrylate intermediate (PLP-dehydroAla) [enzyme]-S-sulfanylcysteine Ketimine intermediate (PLP-Ala) Quinonoid intermediate (PLP-Ala) External aldimine intermediate (PLP-L-Ala)
Type aromatic ring (with nitrogen atoms),phosphate group/phosphate ion amino acids,sulfhydryl group others amino acids others,sulfhydryl group
ChEBI 18405
17561
35235
16977
57972
PubChem 1051
5862
6419722
5950
7311724
1p3wA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1p3wB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3lvjA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3lvjB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3lvkA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3lvlB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3lvmA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3lvmB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1ecxA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Bound:CYS_502 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1ecxB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Bound:CYS_503 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1eg5A01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1eg5B01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1t3iA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1t3iB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1p3wA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:PLP Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1p3wB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:PLP Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3lvjA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:PLP Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3lvjB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:PLP Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3lvkA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:PLP Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3lvlB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:PLP Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3lvmA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:PLP Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3lvmB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:PLP Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1ecxA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:PLP Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1ecxB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:PLP Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1eg5A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:PLP Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1eg5B02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:PLP Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1t3iA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:PLP Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1t3iB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:PLP Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
literature[3],[8],[9]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1p3wA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain invisible 328-333
1p3wB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain invisible 328-333
3lvjA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain invisible 327-332
3lvjB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain CYS 328 invisible 329-332
3lvkA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain CYS 328 invisible 329-332
3lvlB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain invisible 328-332
3lvmA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain invisible 328-332
3lvmB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain invisible 328-332
1ecxA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain invisible 321-332
1ecxB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain invisible 321-331
1eg5A01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain invisible 321-332
1eg5B01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain invisible 321-331
1t3iA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain CYS 372
1t3iB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain CYS 372
1p3wA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 104;ASP 180;GLN 183;LYS 206 LYS 206(PLP binding)
1p3wB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 104;ASP 180;GLN 183;LYS 206 LYS 206(PLP binding)
3lvjA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 104;ASP 180;GLN 183;LYS 206 LYS 206(PLP binding)
3lvjB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 104;ASP 180;GLN 183;LYS 206 LYS 206(PLP binding)
3lvkA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 104;ASP 180;GLN 183;LYS 206 LYS 206(PLP binding)
3lvlB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 104;ASP 180;GLN 183;LYS 206 LYS 206(PLP binding)
3lvmA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 104;ASP 180;GLN 183;LYS 206 LYS 206(PLP binding)
3lvmB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 104;ASP 180;GLN 183;LYS 206 LYS 206(PLP binding)
1ecxA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 99;ASP 177;GLN 180;LYS 203 LYS 203(PLP binding)
1ecxB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 99;ASP 177;GLN 180;LYS 203 LYS 203(PLP binding)
1eg5A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 99;ASP 177;GLN 180;LYS 203 LYS 203(PLP binding)
1eg5B02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 99;ASP 177;GLN 180;LYS 203 LYS 203(PLP binding)
1t3iA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 128;ASP 205;GLN 208;LYS 231 LYS 231(PLP binding)
1t3iB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 128;ASP 205;GLN 208;LYS 231 LYS 231(PLP binding)

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[1]
SCHEME3, p.4719
[3]
SCHEME1, p.459-460

References
[1]
Resource
Comments
Medline ID
PubMed ID 8161529
Journal Biochemistry
Year 1994
Volume 33
Pages 4714-20
Authors Zheng L, White RH, Cash VL, Dean DR
Title Mechanism for the desulfurization of L-cysteine catalyzed by the nifS gene product.
Related PDB
Related UniProtKB
[2]
Resource
Comments PROTEIN SEQUENCE OF 1-9, MUTAGENESIS OF CYS-328.
Medline ID
PubMed ID 10739946
Journal J Biochem
Year 2000
Volume 127
Pages 559-67
Authors Mihara H, Kurihara T, Yoshimura T, Esaki N
Title Kinetic and mutational studies of three NifS homologs from Escherichia coli: mechanistic difference between L-cysteine desulfurase and L-selenocysteine lyase reactions.
Related PDB
Related UniProtKB
[3]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS), ACTIVE SITE, AND PYRIDOXAL PHOSPHATE AT LYS-203.
Medline ID
PubMed ID 10715213
Journal J Mol Biol
Year 2000
Volume 297
Pages 451-64
Authors Kaiser JT, Clausen T, Bourenkow GP, Bartunik HD, Steinbacher S, Huber R
Title Crystal structure of a NifS-like protein from Thermotoga maritima: implications for iron sulphur cluster assembly.
Related PDB 1ecx 1eg5
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 11577100
Journal J Biol Chem
Year 2001
Volume 276
Pages 44521-6
Authors Urbina HD, Silberg JJ, Hoff KG, Vickery LE
Title Transfer of sulfur from IscS to IscU during Fe/S cluster assembly.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 11825893
Journal J Biol Chem
Year 2002
Volume 277
Pages 12868-73
Authors Yang W, Rogers PA, Ding H
Title Repair of nitric oxide-modified ferredoxin [2Fe-2S] cluster by cysteine desulfurase (IscS).
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 11972033
Journal Proc Natl Acad Sci U S A
Year 2002
Volume 99
Pages 5948-52
Authors Kato S, Mihara H, Kurihara T, Takahashi Y, Tokumoto U, Yoshimura T, Esaki N
Title Cys-328 of IscS and Cys-63 of IscU are the sites of disulfide bridge formation in a covalently bound IscS/IscU complex: implications for the mechanism of iron-sulfur cluster assembly.
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 12382038
Journal Appl Microbiol Biotechnol
Year 2002
Volume 60
Pages 12-23
Authors Mihara H, Esaki N
Title Bacterial cysteine desulfurases: their function and mechanisms.
Related PDB
Related UniProtKB
[8]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS), PYRIDOXAL PHOSPHATE AT LYS-206, SUBUNIT, ACTIVE SITE CYS-328.
Medline ID
PubMed ID 12860127
Journal J Mol Biol
Year 2003
Volume 330
Pages 1049-59
Authors Cupp-Vickery JR, Urbina H, Vickery LE
Title Crystal structure of IscS, a cysteine desulfurase from Escherichia coli.
Related PDB 1p3w
Related UniProtKB
[9]
Resource
Comments X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS), PYRIDOXAL PHOSPHATE AT LYS-231, ACTIVE SITE CYS-372.
Medline ID
PubMed ID 15379559
Journal Biochemistry
Year 2004
Volume 43
Pages 12210-9
Authors Tirupati B, Vey JL, Drennan CL, Bollinger JM Jr
Title Kinetic and structural characterization of Slr0077/SufS, the essential cysteine desulfurase from Synechocystis sp. PCC 6803.
Related PDB 1t3i
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID 19883076
Journal Biochemistry
Year 2009
Volume 48
Pages 12014-23
Authors Behshad E, Bollinger JM Jr
Title Kinetic analysis of cysteine desulfurase CD0387 from Synechocystis sp. PCC 6803: formation of the persulfide intermediate.
Related PDB
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID 19308466
Journal J Biol Inorg Chem
Year 2009
Volume 14
Pages 829-39
Authors Nuth M, Cowan JA
Title Iron-sulfur cluster biosynthesis: characterization of IscU-IscS complex formation and a structural model for sulfide delivery to the [2Fe-2S] assembly site.
Related PDB
Related UniProtKB
[12]
Resource
Comments
Medline ID
PubMed ID 19946146
Journal J Biol Chem
Year 2010
Volume 285
Pages 2302-8
Authors Zhang W, Urban A, Mihara H, Leimkuhler S, Kurihara T, Esaki N
Title IscS functions as a primary sulfur-donating enzyme by interacting specifically with MoeB and MoaD in the biosynthesis of molybdopterin in Escherichia coli.
Related PDB
Related UniProtKB
[13]
Resource
Comments
Medline ID
PubMed ID 20404999
Journal PLoS Biol
Year 2010
Volume 8
Pages e1000354
Authors Shi R, Proteau A, Villarroya M, Moukadiri I, Zhang L, Trempe JF, Matte A, Armengod ME, Cygler M
Title Structural basis for Fe-S cluster assembly and tRNA thiolation mediated by IscS protein-protein interactions.
Related PDB 3lvj 3lvk 3lvl 3lvm
Related UniProtKB

Comments
This enzyme catalyzes the elimination of sulfur from L-cysteine to produce L-alanine and sulfane sulfur, via a labile enzyme cysteinyl persulfide intermediate, utilizing pyridoxal 5'-phosphate (PLP). The persulfide sulfur is subsequently transferred to other proteins, such as iron-sulfur containing proteins, proteins related to sulfur-containing cofactor (thiamine, molybdopterin, biotin and lipoic acid) (see [7], [11], [12] and [13]).
This enzyme catalyzes the following reactions (see [3], [10]):
(A) Formation of external aldimine of PLP with amine group of L-cysteine (I00165) (from the internal aldimine with Lys).
(B) Isomerization of the Cys external aldimine to form a Cys ketimine intermediate(I00167), via a Cys quinonoid transition state (I00166).
(C) Transfer of thiol group from the ketimine intermediate (I00167) to active-site Cys, forming a persulfide intermediate (C15812) and an aminoacrylate intermediate (I00171).
(D) Isomerization of the aminoacrylate intermediate (I00171), to form an Ala ketimine intermediate (I00030).
(E) Isomerization of the Ala ketimine intermediate(I00030) to form an Ala external aldimine(I00049), via an Ala quinonoid transition state (I00032).
(F) Formation of internal aldimine of PLP with active-site Lys (from the external aldimine (I00049), releasing L-Ala from PLP.
(G) Transfer of thiol group from the persulfide intermediate (C15812) to the acceptor protein.
####
Acording to the literature [3] and [8], the catalytic residues play the following roles:
Asp205 and Gln208 (of 1t3i) may modulate the activity of PLP.
His128 might act as a general acid/base to protonate either PLP or Cys ketimine intermediate, deprotonate the thiol group of the active-site Cys, and protonate the aminoacrylate intermediate (I00171).
Lys231 may also act as a general acid/base to deprotonate and protonate the external aldimine intermediates (I00165 and I00049).
Cys372 acts as a nucleophile to accept the thiol group from the Cys ketimine intermediate(I00167), and transfers it to the acceptor protein.

Created Updated
2013-07-24 2013-11-14