DB code: D00264

CATH domain 3.40.50.1100 : Rossmann fold
3.40.50.1100 : Rossmann fold Catalytic domain
E.C. 2.5.1.47
CSA 1oas
M-CSA 1oas
MACiE

CATH domain Related DB codes (homologues)
3.40.50.1100 : Rossmann fold T00088 T00089

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
P0A1E3 Cysteine synthase A
EC 2.5.1.47
O-acetylserine sulfhydrylase A
CSase A
O-acetylserine (Thiol)-lyase A
NP_461365.1 (Protein)
NC_003197.1 (DNA/RNA sequence)
PF00291 (PALP)
[Graphical View]

KEGG enzyme name
cysteine synthase
O-acetyl-L-serine sulfhydrylase
O-acetyl-L-serine sulfohydrolase
O-acetylserine (thiol)-lyase
O-acetylserine (thiol)-lyase A
O-acetylserine sulfhydrylase
O3-acetyl-L-serine acetate-lyase (adding hydrogen-sulfide)
acetylserine sulfhydrylase
cysteine synthetase
S-sulfocysteine synthase
3-O-acetyl-L-serine:hydrogen-sulfide2-amino-2-carboxyethyltransferase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P0A1E3 CYSK_SALTY O(3)-acetyl-L-serine + H(2)S = L-cysteine + acetate. Homodimer. Pyridoxal phosphate.

KEGG Pathways
Map code Pathways E.C.
MAP00272 Cysteine metabolism
MAP00450 Selenoamino acid metabolism
MAP00920 Sulfur metabolism

Compound table
Cofactors Substrates Products Intermediates
KEGG-id C00018 C00979 C00283 C00097 C00033
E.C.
Compound Pyridoxal phosphate O3-Acetyl-L-serine Hydrogen sulfide L-Cysteine Acetate
Type aromatic ring (with nitrogen atoms),phosphate group/phosphate ion amino acids,carbohydrate sulfhydryl group amino acids,sulfhydryl group carboxyl group
ChEBI 18405
 18405
 		17981
 58340
 17981
 58340
 		16136
 16136
 		17561
 35235
 17561
 35235
 		15366
 15366
PubChem 1051
 1051
 		6971051
 99478
 6971051
 99478
 		18779926
 402
 18779926
 402
 		5862
 6419722
 5862
 6419722
 		176
 21980959
 176
 21980959
1d6sA01 Unbound Unbound Unbound Unbound Unbound Unbound
1d6sB01 Unbound Unbound Unbound Unbound Unbound Unbound
1fcjA01 Unbound Unbound Unbound Unbound Unbound Unbound
1fcjB01 Unbound Unbound Unbound Unbound Unbound Unbound
1fcjC01 Unbound Unbound Unbound Unbound Unbound Unbound
1fcjD01 Unbound Unbound Unbound Unbound Unbound Unbound
1oasA01 Unbound Unbound Unbound Unbound Unbound Unbound
1oasB01 Unbound Unbound Unbound Unbound Unbound Unbound
1d6sA02 Bound:PLP Unbound Unbound Unbound Unbound Intermediate-analogue:MET-PLP
1d6sB02 Bound:PLP Unbound Unbound Unbound Unbound Intermediate-analogue:PLP-MET
1fcjA02 Bound:PLP Unbound Analogue:SO4 Unbound Unbound Unbound
1fcjB02 Bound:PLP Unbound Analogue:SO4 Unbound Unbound Unbound
1fcjC02 Bound:PLP Unbound Analogue:SO4 Unbound Unbound Unbound
1fcjD02 Bound:PLP Unbound Analogue:SO4 Unbound Unbound Unbound
1oasA02 Bound:PLP Unbound Unbound Unbound Unbound Unbound
1oasB02 Bound:PLP Unbound Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
PDB;1oas & literature [9] & [19]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1d6sA01 ARG 34;ILE 267;LEU 268(Allosteric anion-binding site)
1d6sB01 ARG 34;ILE 267;LEU 268(Allosteric anion-binding site)
1fcjA01 ARG 34;ILE 267;LEU 268(Allosteric anion-binding site)
1fcjB01 ARG 34;ILE 267;LEU 268(Allosteric anion-binding site)
1fcjC01 ARG 34;ILE 267;LEU 268(Allosteric anion-binding site)
1fcjD01 ARG 34;ILE 267;LEU 268(Allosteric anion-binding site)
1oasA01 ARG 34;ILE 267;LEU 268(Allosteric anion-binding site)
1oasB01 ARG 34;ILE 267;LEU 268(Allosteric anion-binding site)
1d6sA02 mutant K41A
1d6sB02 mutant K41A
1fcjA02 LYS 41
1fcjB02 LYS 41
1fcjC02 LYS 41
1fcjD02 LYS 41
1oasA02 LYS 41
1oasB02 LYS 41

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[2]
Scheme I, p.2301-2303 6
[6]
Scheme 1, Scheme 3
[7]
Scheme 3 p.12319-12320, p.12321
[8]
Scheme 4A, p.6364, Scheme 5
[9]
[10]
Scheme 1, p.4780-4782 7
[12]
Scheme 1, p.15424-15427 6
[13]
Scheme 1, p.126-128 5
[14]
Scheme 1 4
[16]
Scheme 1, Scheme 2, p.946-949
[19]
p.283-284

References
[1]
Resource
Comments
Medline ID
PubMed ID 398768
Journal Ciba Found Symp
Year 1979
Volume (72)
Pages 87-99
Authors Kredich NM, Hulanicka MD, Hallquist SG
Title Synthesis of L-cysteine in Salmonella typhimurium.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 1540585
Journal Biochemistry
Year 1992
Volume 31
Pages 2298-303
Authors Cook PF, Hara S, Nalabolu S, Schnackerz KD
Title pH dependence of the absorbance and 31P NMR spectra of O-acetylserine sulfhydrylase in the absence and presence of O-acetyl-L-serine.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 8518286
Journal Biochemistry
Year 1993
Volume 32
Pages 6433-42
Authors Tai CH, Nalabolu SR, Jacobson TM, Minter DE, Cook PF
Title Kinetic mechanisms of the A and B isozymes of O-acetylserine sulfhydrylase from Salmonella typhimurium LT-2 using the natural and alternative reactants.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 8515470
Journal J Mol Biol
Year 1993
Volume 231
Pages 1130-2
Authors Rao GS, Mottonen J, Goldsmith EJ, Cook PF
Title Crystallization and preliminary X-ray data for the A-isozyme of O-acetylserine sulfhydrylase from Salmonella typhimurium.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 7503562
Journal Arch Biochem Biophys
Year 1995
Volume 324
Pages 71-7
Authors Schnackerz KD, Cook PF
Title Resolution of pyridoxal 5'-phosphate from O-acetylserine sulfhydrylase from Salmonella typhimurium and reconstitution of apoenzyme with cofactor and cofactor analogues as a probe of the cofactor binding site.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 7547955
Journal Biochemistry
Year 1995
Volume 34
Pages 12152-60
Authors Schnackerz KD, Tai CH, Simmons JW 3rd, Jacobson TM, Rao GS, Cook PF
Title Identification and spectral characterization of the external aldimine of the O-acetylserine sulfhydrylase reaction.
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 7547974
Journal Biochemistry
Year 1995
Volume 34
Pages 12311-22
Authors Tai CH, Nalabolu SR, Simmons JW 3rd, Jacobson TM, Cook PF
Title Acid-base chemical mechanism of O-acetylserine sulfhydrylases-A and -B from pH studies.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 8639581
Journal Biochemistry
Year 1996
Volume 35
Pages 6358-65
Authors Hwang CC, Woehl EU, Minter DE, Dunn MF, Cook PF
Title Kinetic isotope effects as a probe of the beta-elimination reaction catalyzed by O-acetylserine sulfhydrylase.
Related PDB
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 8873618
Journal Biochemistry
Year 1996
Volume 35
Pages 13485-93
Authors Rege VD, Kredich NM, Tai CH, Karsten WE, Schnackerz KD, Cook PF
Title A change in the internal aldimine lysine (K42) in O-acetylserine sulfhydrylase to alanine indicates its importance in transimination and as a general base catalyst.
Related PDB
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID 8664267
Journal Biochemistry
Year 1996
Volume 35
Pages 4776-83
Authors Woehl EU, Tai CH, Dunn MF, Cook PF
Title Formation of the alpha-aminoacrylate immediate limits the overall reaction catalyzed by O-acetylserine sulfhydrylase.
Related PDB
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID 8617276
Journal Eur J Biochem
Year 1996
Volume 236
Pages 272-82
Authors Rolland N, Ruffet ML, Job D, Douce R, Droux M
Title Spinach chloroplast 0-acetylserine (thiol)-lyase exhibits two catalytically non-equivalent pyridoxal-5'-phosphate-containing active sites.
Related PDB
Related UniProtKB
[12]
Resource
Comments
Medline ID
PubMed ID 9398272
Journal Biochemistry
Year 1997
Volume 36
Pages 15419-27
Authors Benci S, Vaccari S, Mozzarelli A, Cook PF
Title Time-resolved fluorescence of O-acetylserine sulfhydrylase catalytic intermediates.
Related PDB
Related UniProtKB
[13]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS), AND REVISIONS TO 266-267.
Medline ID 98437375
PubMed ID 9761678
Journal J Mol Biol
Year 1998
Volume 283
Pages 121-33
Authors Burkhard P, Rao GS, Hohenester E, Schnackerz KD, Cook PF, Jansonius JN
Title Three-dimensional structure of O-acetylserine sulfhydrylase from Salmonella typhimurium.
Related PDB 1oas
Related UniProtKB P0A1E3
[14]
Resource
Comments
Medline ID
PubMed ID 9761679
Journal J Mol Biol
Year 1998
Volume 283
Pages 135-46
Authors Mozzarelli A, Bettati S, Pucci AM, Burkhard P, Cook PF
Title Catalytic competence of O-acetylserine sulfhydrylase in the crystal probed by polarized absorption microspectrophotometry.
Related PDB
Related UniProtKB
[15]
Resource
Comments
Medline ID
PubMed ID 9914259
Journal Curr Opin Struct Biol
Year 1998
Volume 8
Pages 759-69
Authors Jansonius JN
Title Structure, evolution and action of vitamin B6-dependent enzymes.
Related PDB
Related UniProtKB
[16]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS).
Medline ID 99384139
PubMed ID 10452898
Journal J Mol Biol
Year 1999
Volume 291
Pages 941-53
Authors Burkhard P, Tai CH, Ristroph CM, Cook PF, Jansonius JN
Title Ligand binding induces a large conformational change in O-acetylserine sulfhydrylase from Salmonella typhimurium.
Related PDB 1d6s
Related UniProtKB P0A1E3
[17]
Resource
Comments
Medline ID
PubMed ID 11193402
Journal Biosci Biotechnol Biochem
Year 2000
Volume 64
Pages 2352-9
Authors Sugihara Y, Yamagata S, Mizuno Y, Ezaki T
Title Characterization of O-acetyl-L-serine sulfhydrylase purified from an alkaliphilic bacterium.
Related PDB
Related UniProtKB
[18]
Resource
Comments
Medline ID
PubMed ID 10995767
Journal J Biol Chem
Year 2000
Volume 275
Pages 40244-51
Authors Bettati S, Benci S, Campanini B, Raboni S, Chirico G, Beretta S, Schnackerz KD, Hazlett TL, Gratton E, Mozzarelli A
Title Role of pyridoxal 5'-phosphate in the structural stabilization of O-acetylserine sulfhydrylase.
Related PDB
Related UniProtKB
[19]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS).
Medline ID 20481415
PubMed ID 11023792
Journal J Mol Biol
Year 2000
Volume 303
Pages 279-86
Authors Burkhard P, Tai CH, Jansonius JN, Cook PF
Title Identification of an allosteric anion-binding site on O-acetylserine sulfhydrylase: structure of the enzyme with chloride bound.
Related PDB 1fcj
Related UniProtKB P0A1E3
[20]
Resource
Comments
Medline ID
PubMed ID 10673430
Journal Structure Fold Des
Year 2000
Volume 8
Pages R1-6
Authors Schneider G, Kack H, Lindqvist Y
Title The manifold of vitamin B6 dependent enzymes.
Related PDB
Related UniProtKB
[21]
Resource
Comments
Medline ID
PubMed ID 11412097
Journal Biochemistry
Year 2001
Volume 40
Pages 7446-52
Authors Tai CH, Burkhard P, Gani D, Jenn T, Johnson C, Cook PF
Title Characterization of the allosteric anion-binding site of O-acetylserine sulfhydrylase.
Related PDB
Related UniProtKB
[22]
Resource
Comments
Medline ID
PubMed ID 11259310
Journal Biophys J
Year 2001
Volume 80
Pages 1973-85
Authors Chirico G, Bettati S, Mozzarelli A, Chen Y, Muller JD, Gratton E
Title Molecular heterogeneity of O-acetylserine sulfhydrylase by two-photon excited fluorescence fluctuation spectroscopy.
Related PDB
Related UniProtKB
[23]
Resource
Comments
Medline ID
PubMed ID 11168407
Journal Eur J Biochem
Year 2001
Volume 268
Pages 686-93
Authors Wirtz M, Berkowitz O, Droux M, Hell R
Title The cysteine synthase complex from plants. Mitochondrial serine acetyltransferase from Arabidopsis thaliana carries a bifunctional domain for catalysis and protein-protein interaction.
Related PDB
Related UniProtKB

Comments
This enzyme was transferred from E.C. 4.2.99.8 to E.C. 2.5.1.47.
This enzyme belongs to the type-II PLP-dependent enzyme superfamily (or Tryptophan synthase beta-subunit family), according to the literature [15] & [20].
According to the literature [7], [8], [10], [12] & [13], this enzyme catalyzes the following reactions:
(A) Formation of external aldimine (with amine group of the first substrate, O-acetyl-serine, OAS).
(B) Isomerization (change in the position of double-bond).
(C) beta-elimination of acetyl group, forming a double-bonded beta-carbon (bound to PLP), and releasing acetate.
(D) Addition of the second substrate, sulfide, to the double-bonded beta-carbon.
(E) Isomerization (change in the position of double-bond).
(F) Formation of internal aldimine, releasing the product.

Created Updated
2004-07-15 2009-02-26