PDBsum entry 1yml

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Hydrolase, cell cycle PDB id
Protein chain
171 a.a. *
Waters ×172
* Residue conservation analysis
PDB id:
Name: Hydrolase, cell cycle
Title: Crystal structure of the cdc25b phosphatase catalytic domain with the active site cysteine in the sulfenic form
Structure: M-phase inducer phosphatase 2. Chain: a. Fragment: catalytic domain. Synonym: cdc25b phosphatase. Dual specificity phosphatase cdc25b. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: cdc25b, cdc25hu2. Expressed in: escherichia coli. Expression_system_taxid: 562
1.70Å     R-factor:   0.191     R-free:   0.208
Authors: G.K.Buhrman,B.Parker,J.Sohn,J.Rudolph,C.Mattos
Key ref:
G.Buhrman et al. (2005). Structural mechanism of oxidative regulation of the phosphatase Cdc25B via an intramolecular disulfide bond. Biochemistry, 44, 5307-5316. PubMed id: 15807524 DOI: 10.1021/bi047449f
21-Jan-05     Release date:   12-Apr-05    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P30305  (MPIP2_HUMAN) -  M-phase inducer phosphatase 2
580 a.a.
171 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 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: 10.1021/bi047449f Biochemistry 44:5307-5316 (2005)
PubMed id: 15807524  
Structural mechanism of oxidative regulation of the phosphatase Cdc25B via an intramolecular disulfide bond.
G.Buhrman, B.Parker, J.Sohn, J.Rudolph, C.Mattos.
Cdc25B phosphatase, an important regulator of the cell cycle, forms an intramolecular disulfide bond in response to oxidation leading to reversible inactivation of phosphatase activity. We have obtained a crystallographic time course revealing the structural rearrangements that occur in the P-loop as the enzyme goes from its apo state, through the sulfenic (Cys-SO(-)) intermediate, to the stable disulfide. We have also obtained the structures of the irreversibly oxidized sulfinic (Cys-SO(2)(-)) and sulfonic (Cys-SO(3)(-)) Cdc25B. The active site P-loop is found in three conformations. In the apoenzyme, the P-loop is in the active conformation. In the sulfenic intermediate, the P-loop partially obstructs the active site cysteine, poised to undergo the conformational changes that accompany disulfide bond formation. In the disulfide form, the P-loop is closed over the active site cysteine, resulting in an enzyme that is unable to bind substrate. The structural changes that occur in the sulfenic intermediate of Cdc25B are distinctly different from those seen in protein tyrosine phosphatase 1B where a five-membered sulfenyl amide ring is generated as the stable end product. This work elucidates the mechanism by which chemistry and structure are coupled in the regulation of Cdc25B by reactive oxygen species.

Literature references that cite this PDB file's key reference

  PubMed id Reference
21185243 M.Bruschi, G.Candiano, L.D.Ciana, A.Petretto, L.Santucci, M.Prunotto, R.Camilla, R.Coppo, and G.M.Ghiggeri (2011).
Analysis of the oxido-redox status of plasma proteins. Technology advances for clinical applications.
  J Chromatogr B Analyt Technol Biomed Life Sci, 879, 1338-1344.  
19634988 M.A.Wouters, S.W.Fan, and N.L.Haworth (2010).
Disulfides as redox switches: from molecular mechanisms to functional significance.
  Antioxid Redox Signal, 12, 53-91.  
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
19598234 S.W.Fan, R.A.George, N.L.Haworth, L.L.Feng, J.Y.Liu, and M.A.Wouters (2009).
Conformational changes in redox pairs of protein structures.
  Protein Sci, 18, 1745-1765.  
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.  
18500784 K.Keerthi, S.Sivaramakrishnan, and K.S.Gates (2008).
Evidence for a Morin type intramolecular cyclization of an alkene with a phenylsulfenic acid group in neutral aqueous solution.
  Chem Res Toxicol, 21, 1368-1374.  
18573100 R.J.Gruninger, L.Brent Selinger, and S.C.Mosimann (2008).
Effect of ionic strength and oxidation on the P-loop conformation of the protein tyrosine phosphatase-like phytase, PhyAsr.
  FEBS J, 275, 3783-3792.
PDB codes: 2psz 2pt0 3d1h 3d1o 3d1q
17567745 A.A.Puhl, R.J.Gruninger, R.Greiner, T.W.Janzen, S.C.Mosimann, and L.B.Selinger (2007).
Kinetic and structural analysis of a bacterial protein tyrosine phosphatase-like myo-inositol polyphosphatase.
  Protein Sci, 16, 1368-1378.
PDB codes: 2b4o 2b4p 2b4u
17174465 J.Sohn, and J.Rudolph (2007).
Temperature dependence of binding and catalysis for the Cdc25B phosphatase.
  Biophys Chem, 125, 549-555.  
17130129 N.Nagahara, T.Yoshii, Y.Abe, and T.Matsumura (2007).
Thioredoxin-dependent enzymatic activation of mercaptopyruvate sulfurtransferase. An intersubunit disulfide bond serves as a redox switch for activation.
  J Biol Chem, 282, 1561-1569.  
17239398 P.Liu, H.E.Ewis, P.C.Tai, C.D.Lu, and I.T.Weber (2007).
Crystal structure of the Geobacillus stearothermophilus carboxylesterase Est55 and its activation of prodrug CPT-11.
  J Mol Biol, 367, 212-223.
PDB codes: 2ogs 2ogt
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.  
16288457 G.Hible, P.Christova, L.Renault, E.Seclaman, A.Thompson, E.Girard, H.Munier-Lehmann, and J.Cherfils (2006).
Unique GMP-binding site in Mycobacterium tuberculosis guanosine monophosphate kinase.
  Proteins, 62, 489-500.
PDB codes: 1znw 1znx 1zny 1znz
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.  
16677071 J.R.Stone, and S.Yang (2006).
Hydrogen peroxide: a signaling messenger.
  Antioxid Redox Signal, 8, 243-270.  
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.