EzCatDB: S00393
Related links:    PDB-formatted query search system Fasta-formatted query search system Fasta-formatted query search system

DB codeS00393
RLCP classification1.15.36100.51 : Hydrolysis
CATH domainDomain 13.40.250.10 : Oxidized Rhodanese; domain 1Catalytic domain
E.C.3.1.3.48


Enzyme Name
UniProtKBKEGG

P30304P30305
Protein nameM-phase inducer phosphatase 1M-phase inducer phosphatase 2protein-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
SynonymsEC 3.1.3.48
Dual specificity phosphatase Cdc25A
EC 3.1.3.48
Dual specificity phosphatase Cdc25B
RefSeqNP_001780.2 (Protein)
NM_001789.2 (DNA/RNA sequence)
NP_963861.1 (Protein)
NM_201567.1 (DNA/RNA sequence)
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)
PfamPF06617 (M-inducer_phosp)
PF00581 (Rhodanese)
[Graphical view]
PF06617 (M-inducer_phosp)
PF00581 (Rhodanese)
[Graphical view]


UniProtKB:Accession NumberP30304P30305
Entry nameMPIP1_HUMANMPIP2_HUMAN
ActivityProtein tyrosine phosphate + H(2)O = protein tyrosine + phosphate.Protein tyrosine phosphate + H(2)O = protein tyrosine + phosphate.
SubunitInteracts 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.
Subcellular location
Centrosome.
Cofactor


Compound table: links to PDB-related databases & PoSSuM

SubstratesProducts
KEGG-idC01167C00001C00585C00009
CompoundProtein tyrosine phosphateH2OProtein tyrosineOrthophosphate
Typearomatic ring (only carbon atom),peptide/protein,phosphate group/phosphate ionH2Oaromatic ring (only carbon atom),peptide/proteinphosphate group/phosphate ion
ChEBI
15377

26078
PubChem
962
22247451

22486802
1004
            
1c25AUnbound UnboundUnbound
1cwrAUnbound UnboundUnbound
1qb0AUnbound UnboundAnalogue:SO4

Active-site residues
resource
literature [2],[3]
pdbCatalytic residues
         
1c25ACYS 430;GLU 431;SER 433;ARG 436
1cwrACYS 473;GLU 474;SER 476;ARG 479
1qb0ACYS 473;GLU 474;SER 476;ARG 479

References for Catalytic Mechanism
ReferencesSectionsNo. 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.53
[9]Fig.94

references
[1]
PubMed ID8771191
JournalProtein Sci
Year1996
Volume5
Pages5-12
AuthorsEckstein JW, Beer-Romero P, Berdo I
TitleIdentification of an essential acidic residue in Cdc25 protein phosphatase and a general three-dimensional model for a core region in protein phosphatases.
[2]
PubMed ID8617791
JournalJ Biol Chem
Year1996
Volume271
Pages5118-24
AuthorsXu X, Burke SP
TitleRoles of active site residues and the NH2-terminal domain in the catalysis and substrate binding of human Cdc25.
[3]
CommentsX-ray crystallography (2.3 Angstroms)
PubMed ID9604936
JournalCell
Year1998
Volume93
Pages617-625
AuthorsFauman EB, Cogswell JP, Lovejoy B, Rocque WJ, Holmes W, Montana VG, Piwnica-Worms H, Rink MJ, Saper MA
TitleCrystal structure of the catalytic domain of the human cell cycle control phosphatase, Cdc25A.
Related PDB1c25
Related UniProtKBP30304
[4]
CommentsX-ray crystallography
PubMed ID10543950
JournalJ Mol Biol
Year1999
Volume293
Pages559-568
AuthorsReynolds RA, Yem AW, Wolfe CL, Deibel MR Jr, Chidester CG, Watenpaugh KD
TitleCrystal structure of the catalytic subunit of Cdc25B required for G2/M phase transition of the cell cycle.
Related PDB1cwr,1qb0
[5]
PubMed ID10788330
JournalJ Mol Biol
Year2000
Volume298
Pages691-704
AuthorsBordo D, Deriu D, Colnaghi R, Carpen A, Pagani S, Bolognesi M
TitleThe crystal structure of a sulfurtransferase from Azotobacter vinelandii highlights the evolutionary relationship between the rhodanese and phosphatase enzyme families.
[6]
PubMed ID10978163
JournalBiochemistry
Year2000
Volume39
Pages10781-9
AuthorsChen W, Wilborn M, Rudolph J
TitleDual-specific Cdc25B phosphatase: in search of the catalytic acid.
[7]
PubMed ID11805096
JournalJ Biol Chem
Year2002
Volume277
Pages11190-200
AuthorsMcCain DF, Catrina IE, Hengge AC, Zhang ZY
TitleThe catalytic mechanism of Cdc25A phosphatase.
[8]
PubMed ID12151332
JournalEMBO Rep
Year2002
Volume3
Pages741-6
AuthorsBordo D, Bork P
TitleThe rhodanese/Cdc25 phosphatase superfamily. Sequence-structure-function relations.
[9]
PubMed ID12463761
JournalBiochemistry
Year2002
Volume41
Pages14613-23
AuthorsRudolph J
TitleCatalytic mechanism of Cdc25.

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.

createdupdated
2002-09-272009-02-26


Copyright: Nozomi Nagano, JST & CBRC-AIST
Funded by PRESTO/Japan Science and Technology Corporation (JST) (December 2001 - November 2004)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2006)
Funded by Grant-in-Aid for Scientific Research (B)/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (September 2005 - September 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2011 - March 2012)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2012 - March 2013)
Supported by the commission for the Development of Artificial Gene Synthesis Technology for Creating Innovative Biomaterial from the Ministry of Economy, Trade and Industry (METI) (October 2012 - )
© Biotechnology Research Institute for Drug Discovery, AIST, 2015-2016 All Rights Reserved.
© Computational Biology Research Center, AIST, 2004-2016 All Rights Reserved.