DB code: S00393

RLCP classification 1.15.36100.51 : Hydrolysis
CATH domain 3.40.250.10 : Oxidized Rhodanese; domain 1 Catalytic domain
E.C. 3.1.3.48
CSA
M-CSA
MACiE

CATH domain Related DB codes (homologues)

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
P30304 M-phase inducer phosphatase 1
EC 3.1.3.48
Dual specificity phosphatase Cdc25A
NP_001780.2 (Protein)
NM_001789.2 (DNA/RNA sequence)
NP_963861.1 (Protein)
NM_201567.1 (DNA/RNA sequence)
PF06617 (M-inducer_phosp)
PF00581 (Rhodanese)
[Graphical View]
P30305 M-phase inducer phosphatase 2
EC 3.1.3.48
Dual specificity phosphatase Cdc25B
NP_004349.1 (Protein)
NM_004358.3 (DNA/RNA sequence)
NP_068658.1 (Protein)
NM_021872.2 (DNA/RNA sequence)
NP_068659.1 (Protein)
NM_021873.2 (DNA/RNA sequence)
PF06617 (M-inducer_phosp)
PF00581 (Rhodanese)
[Graphical View]

KEGG enzyme name
protein-tyrosine-phosphatase
phosphotyrosine phosphatase
phosphoprotein phosphatase (phosphotyrosine)
phosphotyrosine histone phosphatase
protein phosphotyrosine phosphatase
tyrosylprotein phosphatase
phosphotyrosine protein phosphatase
phosphotyrosylprotein phosphatase
tyrosine O-phosphate phosphatase
PPT-phosphatase
PTPase
[phosphotyrosine]protein phosphatase
PTP-phosphatase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P30304 MPIP1_HUMAN Protein tyrosine phosphate + H(2)O = protein tyrosine + phosphate. Interacts with CCNB1/cyclin B1. Interacts with YWHAE/14- 3-3 epsilon when phosphorylated. Interacts with CUL1 specifically when CUL1 is neddylated and active. Interacts with BTRC/BTRCP1 and FBXW11/BTRCP2. Interactions with CUL1, BTRC and FBXW11 are enhanced upon DNA damage.
P30305 MPIP2_HUMAN Protein tyrosine phosphate + H(2)O = protein tyrosine + phosphate. Centrosome.

KEGG Pathways
Map code Pathways E.C.

Compound table
Substrates Products Intermediates
KEGG-id C01167 C00001 C00585 C00009
E.C.
Compound Protein tyrosine phosphate H2O Protein tyrosine Orthophosphate
Type aromatic ring (only carbon atom),peptide/protein,phosphate group/phosphate ion H2O aromatic ring (only carbon atom),peptide/protein phosphate group/phosphate ion
ChEBI 15377
26078
PubChem 22247451
962
1004
22486802
1c25A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound
1cwrA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound
1qb0A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Analogue:SO4

Reference for Active-site residues
resource references E.C.
literature [2],[3]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1c25A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain CYS 430;GLU 431;SER 433;ARG 436
1cwrA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain CYS 473;GLU 474;SER 476;ARG 479
1qb0A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain CYS 473;GLU 474;SER 476;ARG 479

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[1]
p.7-8
[2]
p.5119-5120
[3]
p.620-621
[4]
p.561-564
[6]
p.10781
[7]
Fig.4, Fig.5 3
[9]
Fig.9 4

References
[1]
Resource
Comments
Medline ID
PubMed ID 8771191
Journal Protein Sci
Year 1996
Volume 5
Pages 5-12
Authors Eckstein JW, Beer-Romero P, Berdo I
Title Identification of an essential acidic residue in Cdc25 protein phosphatase and a general three-dimensional model for a core region in protein phosphatases.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 8617791
Journal J Biol Chem
Year 1996
Volume 271
Pages 5118-24
Authors Xu X, Burke SP
Title Roles of active site residues and the NH2-terminal domain in the catalysis and substrate binding of human Cdc25.
Related PDB
Related UniProtKB
[3]
Resource
Comments X-ray crystallography (2.3 Angstroms)
Medline ID
PubMed ID 9604936
Journal Cell
Year 1998
Volume 93
Pages 617-625
Authors Fauman EB, Cogswell JP, Lovejoy B, Rocque WJ, Holmes W, Montana VG, Piwnica-Worms H, Rink MJ, Saper MA
Title Crystal structure of the catalytic domain of the human cell cycle control phosphatase, Cdc25A.
Related PDB 1c25
Related UniProtKB P30304
[4]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 10543950
Journal J Mol Biol
Year 1999
Volume 293
Pages 559-568
Authors Reynolds RA, Yem AW, Wolfe CL, Deibel MR Jr, Chidester CG, Watenpaugh KD
Title Crystal structure of the catalytic subunit of Cdc25B required for G2/M phase transition of the cell cycle.
Related PDB 1cwr 1qb0
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 10788330
Journal J Mol Biol
Year 2000
Volume 298
Pages 691-704
Authors Bordo D, Deriu D, Colnaghi R, Carpen A, Pagani S, Bolognesi M
Title The crystal structure of a sulfurtransferase from Azotobacter vinelandii highlights the evolutionary relationship between the rhodanese and phosphatase enzyme families.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 10978163
Journal Biochemistry
Year 2000
Volume 39
Pages 10781-9
Authors Chen W, Wilborn M, Rudolph J
Title Dual-specific Cdc25B phosphatase: in search of the catalytic acid.
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 11805096
Journal J Biol Chem
Year 2002
Volume 277
Pages 11190-200
Authors McCain DF, Catrina IE, Hengge AC, Zhang ZY
Title The catalytic mechanism of Cdc25A phosphatase.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 12151332
Journal EMBO Rep
Year 2002
Volume 3
Pages 741-6
Authors Bordo D, Bork P
Title The rhodanese/Cdc25 phosphatase superfamily. Sequence-structure-function relations.
Related PDB
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 12463761
Journal Biochemistry
Year 2002
Volume 41
Pages 14613-23
Authors Rudolph J
Title Catalytic mechanism of Cdc25.
Related PDB
Related UniProtKB

Comments
According to the literature [3], Cys430 plays a catalytic role, with its thiolate ion, as nucleophile.
Whilst the paper [1] identified Asp383 (PDB; 1c25) as the catalytic acid, another paper [3] reported that Glu431 may act as a general acid. However, more recent papers, [6], [7] & [9], mentioned alternative catalytic mechanisms.
The literature [6] mentioned that the catalytic acid does not seem to be located within the enzym itself, and may lie on its protein substrate.
The paper [7] suggested the two possible catalytic mechanisms dependent on the pKa of the leaving group. In both mechanisms, for the substrates with lower leaving group pKa, the catalysis can proceed without catalytic acid. In contrast, in the first catalytic mechanism model, the attainment of the transition state is so slow that protonation of the leaving group occurs at or before the transition state. On the other hand, in the second model, the conformational change will bring Glu431 (PDB; 1c25) into proper position to serve as a catalytic acid for the higher leaving group pKa substrates.
The most recent literature [9] proposed another catalytic mechanism, in which the monoprotonated phosphate of the protein substrate provides the critical proton to the leaving group. In this proposed mechanism, the residue corresponding to Glu431 (PDB; 1c25) functions as a catalytic base in the transfer of the proton from the phosphate to the leaving group.

Created Updated
2002-09-27 2009-02-26