PDBsum entry 1cwr

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Hydrolase PDB id
Protein chain
178 a.a. *
Waters ×103
* Residue conservation analysis
PDB id:
Name: Hydrolase
Title: Human cdc25b catalytic domain without ion in catalytic site
Structure: Protein (m-phase inducer phosphatase 2 (cdc25b)). Chain: a. Fragment: catalytic domain. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Cellular_location: cytoplasm. Gene: cdc25b. Expressed in: escherichia coli. Expression_system_taxid: 562.
2.10Å     R-factor:   0.204     R-free:   0.224
Authors: K.D.Watenpaugh,R.A.Reynolds,C.G.Chidester
Key ref:
R.A.Reynolds et al. (1999). Crystal structure of the catalytic subunit of Cdc25B required for G2/M phase transition of the cell cycle. J Mol Biol, 293, 559-568. PubMed id: 10543950 DOI: 10.1006/jmbi.1999.3168
26-Aug-99     Release date:   28-Aug-00    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P30305  (MPIP2_HUMAN) -  M-phase inducer phosphatase 2
580 a.a.
178 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - Protein-tyrosine-phosphatase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Protein tyrosine phosphate + H2O = protein tyrosine + phosphate
Protein tyrosine phosphate
+ H(2)O
= protein tyrosine
+ phosphate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     intracellular   1 term 
  Biological process     M phase of mitotic cell cycle   2 terms 
  Biochemical function     protein tyrosine phosphatase activity     1 term  


DOI no: 10.1006/jmbi.1999.3168 J Mol Biol 293:559-568 (1999)
PubMed id: 10543950  
Crystal structure of the catalytic subunit of Cdc25B required for G2/M phase transition of the cell cycle.
R.A.Reynolds, A.W.Yem, C.L.Wolfe, M.R.Deibel, C.G.Chidester, K.D.Watenpaugh.
Cdc25B is a dual specificity phosphatase involved in the control of cyclin-dependent kinases and the progression of cells through the cell cycle. A series of minimal domain Cdc25B constructs maintaining catalytic activity have been expressed. The structure of a minimum domain construct binding sulfate was determined at 1.9 A resolution and a temperature of 100 K. Other forms of the same co?nstruct were determined at lower resolution and room temperature. The overall folding and structure of the domain is similar to that found for Cdc25A. An important difference between the two is that the Cdc25B domain binds oxyanions in the catalytic site while that of Cdc25A appears unable to bind oxyanions. There are also important conformational differences in the C-terminal region. In Cdc25B, both sulfate and tungstate anions are shown to bind in the catalytic site containing the signature motif (HCxxxxxR) in a conformation similar to that of other protein tyrosine phosphatases and dual specificity phosphatases, with the exception of the Cdc25A. The Cdc25B constructs, with various truncations of the C-terminal residues, are shown to have potent catalytic activity. When cut back to the site at which the Cdc25A structure begins to deviate from the Cdc25B structure, the activity is considerably less. There is a pocket extending from the catalytic site to an anion-binding site containing a chloride about 14 A away. The catalytic cysteine residue, Cys473, can be oxidized to form a disulfide linkage to Cys426. A readily modifiable cysteine residue, Cys484, resides in another pocket that binds a sulfate but not in the signature motif conformation. This region of the structure is highly conserved between the Cdc25 molecules and could serve some unknown function.
  Selected figure(s)  
Figure 1.
Figure 1. Alignment of catalytic domains of Cdc25B (construct III) and Cdc25A used in the crystal structure determinations. Disor- dered and secondary domains are indicated above and below the sequences. Residues encircling the catalytic site are underlined.
Figure 2.
Figure 2. Superposition of Cdc25B (green) and Cdc25A (yellow, PDB accession code 1c25) catalytic domains. Groups from Cdc25B structure included with atoms color coded: carbon, green; oxygen, red; sulfur, yellow; and chlorine, white.
  The above figures are reprinted by permission from Elsevier: J Mol Biol (1999, 293, 559-568) copyright 1999.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20740493 G.M.Arantes (2010).
Flexibility and inhibitor binding in cdc25 phosphatases.
  Proteins, 78, 3017-3032.  
19594147 A.B.Mamonov, D.Bhatt, D.J.Cashman, Y.Ding, and D.M.Zuckerman (2009).
General library-based Monte Carlo technique enables equilibrium sampling of semi-atomistic protein models.
  J Phys Chem B, 113, 10891-10904.  
19489729 A.Edwards (2009).
Large-scale structural biology of the human proteome.
  Annu Rev Biochem, 78, 541-568.  
19301836 J.M.Parks, H.Hu, J.Rudolph, and W.Yang (2009).
Mechanism of Cdc25B phosphatase with the small molecule substrate p-nitrophenyl phosphate from QM/MM-MFEP calculations.
  J Phys Chem B, 113, 5217-5224.  
19670211 R.Koike, A.Kidera, and M.Ota (2009).
Alteration of oligomeric state and domain architecture is essential for functional transformation between transferase and hydrolase with the same scaffold.
  Protein Sci, 18, 2060-2066.  
19371084 S.J.Tsai, U.Sen, L.Zhao, W.B.Greenleaf, J.Dasgupta, E.Fiorillo, V.Orrú, N.Bottini, and X.S.Chen (2009).
Crystal structure of the human lymphoid tyrosine phosphatase catalytic domain: insights into redox regulation .
  Biochemistry, 48, 4838-4845.
PDB code: 3h2x
18855677 A.Bakan, J.S.Lazo, P.Wipf, K.M.Brummond, and I.Bahar (2008).
Toward a molecular understanding of the interaction of dual specificity phosphatases with substrates: insights from structure-based modeling and high throughput screening.
  Curr Med Chem, 15, 2536-2544.  
18504625 H.Park, and Y.H.Jeon (2008).
Toward the virtual screening of Cdc25A phosphatase inhibitors with the homology modeled protein structure.
  J Mol Model, 14, 833-841.  
18593226 M.S.Rodrigues, M.M.Reddy, and M.Sattler (2008).
Cell cycle regulation by oncogenic tyrosine kinases in myeloid neoplasias: from molecular redox mechanisms to health implications.
  Antioxid Redox Signal, 10, 1813-1848.  
17287826 J.Rudolph (2007).
Inhibiting transient protein-protein interactions: lessons from the Cdc25 protein tyrosine phosphatases.
  Nat Rev Cancer, 7, 202-211.  
17174465 J.Sohn, and J.Rudolph (2007).
Temperature dependence of binding and catalysis for the Cdc25B phosphatase.
  Biophys Chem, 125, 549-555.  
17443687 L.Sun, Y.Chai, R.Hannigan, V.K.Bhogaraju, and K.Machaca (2007).
Zinc regulates the ability of Cdc25C to activate MPF/cdk1.
  J Cell Physiol, 213, 98.  
16892390 A.Lavecchia, S.Cosconati, V.Limongelli, and E.Novellino (2006).
Modeling of Cdc25B dual specifity protein phosphatase inhibitors: docking of ligands and enzymatic inhibition mechanism.
  ChemMedChem, 1, 540-550.  
  17012788 D.Bisacchi, Y.Zhou, B.P.Rosen, R.Mukhopadhyay, and D.Bordo (2006).
Crystallization and preliminary crystallographic characterization of LmACR2, an arsenate/antimonate reductase from Leishmania major.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 62, 976-979.  
16607668 G.Roos, S.Loverix, E.Brosens, K.Van Belle, L.Wyns, P.Geerlings, and J.Messens (2006).
The activation of electrophile, nucleophile and leaving group during the reaction catalysed by pI258 arsenate reductase.
  Chembiochem, 7, 981-989.  
16680676 M.Hattori, E.Mizohata, A.Tatsuguchi, R.Shibata, S.Kishishita, K.Murayama, T.Terada, S.Kuramitsu, M.Shirouzu, and S.Yokoyama (2006).
Crystal structure of the single-domain rhodanese homologue TTHA0613 from Thermus thermophilus HB8.
  Proteins, 64, 284-287.
PDB code: 1wv9
16865672 Y.Takahashi, J.A.Lavigne, S.D.Hursting, G.V.Chandramouli, S.N.Perkins, Y.S.Kim, and T.T.Wang (2006).
Molecular signatures of soy-derived phytochemicals in androgen-responsive prostate cancer cells: a comparison study using DNA microarray.
  Mol Carcinog, 45, 943-956.  
15822194 A.P.Ducruet, A.Vogt, P.Wipf, and J.S.Lazo (2005).
Dual specificity protein phosphatases: therapeutic targets for cancer and Alzheimer's disease.
  Annu Rev Pharmacol Toxicol, 45, 725-750.  
15890001 A.Salmeen, and D.Barford (2005).
Functions and mechanisms of redox regulation of cysteine-based phosphatases.
  Antioxid Redox Signal, 7, 560-577.  
15576557 D.Pantoja-Uceda, B.López-Méndez, S.Koshiba, M.Inoue, T.Kigawa, T.Terada, M.Shirouzu, A.Tanaka, M.Seki, K.Shinozaki, S.Yokoyama, and P.Güntert (2005).
Solution structure of the rhodanese homology domain At4g01050(175-295) from Arabidopsis thaliana.
  Protein Sci, 14, 224-230.
PDB code: 1vee
15890022 J.Rudolph (2005).
Redox regulation of the Cdc25 phosphatases.
  Antioxid Redox Signal, 7, 761-767.  
15900534 L.Bialy, and H.Waldmann (2005).
Inhibitors of protein tyrosine phosphatases: next-generation drugs?
  Angew Chem Int Ed Engl, 44, 3814-3839.  
15329414 I.Landrieu, M.da Costa, L.De Veylder, F.Dewitte, K.Vandepoele, S.Hassan, J.M.Wieruszeski, F.Corellou, J.D.Faure, M.Van Montagu, D.Inzé, and G.Lippens (2004).
A small CDC25 dual-specificity tyrosine-phosphatase isoform in Arabidopsis thaliana.
  Proc Natl Acad Sci U S A, 101, 13380-13385.
PDB code: 1t3k
15534213 J.Sohn, K.Kristjánsdóttir, A.Safi, B.Parker, B.Kiburz, and J.Rudolph (2004).
Remote hot spots mediate protein substrate recognition for the Cdc25 phosphatase.
  Proc Natl Acad Sci U S A, 101, 16437-16441.  
15324805 K.Kristjánsdóttir, and J.Rudolph (2004).
Cdc25 phosphatases and cancer.
  Chem Biol, 11, 1043-1051.  
14690594 M.J.Begley, G.S.Taylor, S.A.Kim, D.M.Veine, J.E.Dixon, and J.A.Stuckey (2003).
Crystal structure of a phosphoinositide phosphatase, MTMR2: insights into myotubular myopathy and Charcot-Marie-Tooth syndrome.
  Mol Cell, 12, 1391-1402.
PDB codes: 1lw3 1m7r
14559997 M.S.Chen, C.E.Ryan, and H.Piwnica-Worms (2003).
Chk1 kinase negatively regulates mitotic function of Cdc25A phosphatase through 14-3-3 binding.
  Mol Cell Biol, 23, 7488-7497.  
12384979 B.I.Carr, Z.Wang, and S.Kar (2002).
K vitamins, PTP antagonism, and cell growth arrest.
  J Cell Physiol, 193, 263-274.  
12151332 D.Bordo, and P.Bork (2002).
The rhodanese/Cdc25 phosphatase superfamily. Sequence-structure-function relations.
  EMBO Rep, 3, 741-746.  
11805096 D.F.McCain, I.E.Catrina, A.C.Hengge, and Z.Y.Zhang (2002).
The catalytic mechanism of Cdc25A phosphatase.
  J Biol Chem, 277, 11190-11200.  
12461518 M.A.Lyon, A.P.Ducruet, P.Wipf, and J.S.Lazo (2002).
Dual-specificity phosphatases as targets for antineoplastic agents.
  Nat Rev Drug Discov, 1, 961-976.  
11925443 P.A.Savitsky, and T.Finkel (2002).
Redox regulation of Cdc25C.
  J Biol Chem, 277, 20535-20540.  
11986303 T.S.Chang, W.Jeong, S.Y.Choi, S.Yu, S.W.Kang, and S.G.Rhee (2002).
Regulation of peroxiredoxin I activity by Cdc2-mediated phosphorylation.
  J Biol Chem, 277, 25370-25376.  
11709175 A.Spallarossa, J.L.Donahue, T.J.Larson, M.Bolognesi, and D.Bordo (2001).
Escherichia coli GlpE is a prototype sulfurtransferase for the single-domain rhodanese homology superfamily.
  Structure, 9, 1117-1125.
PDB codes: 1gmx 1gn0
11592406 D.Bordo, F.Forlani, A.Spallarossa, R.Colnaghi, A.Carpen, M.Bolognesi, and S.Pagani (2001).
A persulfurated cysteine promotes active site reactivity in Azotobacter vinelandii Rhodanese.
  Biol Chem, 382, 1245-1252.
PDB codes: 1h4k 1h4m
11689696 Z.Q.Ma, Z.Liu, E.S.Ngan, and S.Y.Tsai (2001).
Cdc25B functions as a novel coactivator for the steroid receptors.
  Mol Cell Biol, 21, 8056-8067.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.