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PDBsum entry 1m3g

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protein links
Hydrolase PDB id
1m3g
Jmol
Contents
Protein chain
145 a.a. *
* Residue conservation analysis
PDB id:
1m3g
Name: Hydrolase
Title: Solution structure of the catalytic domain of mapk phosphatase pac-1: insights into substrate-induced enzymatic activation
Structure: Dual specificity protein phosphatase 2. Chain: a. Fragment: catalytic domain, residues 170-314. Synonym: mapk phosphatase pac-1, dual specificity protein phosphatase pac-1. Engineered: yes. Mutation: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.
NMR struc: 1 models
Authors: A.Farooq,M.-M.Zhou
Key ref:
A.Farooq et al. (2003). Solution structure of the MAPK phosphatase PAC-1 catalytic domain. Insights into substrate-induced enzymatic activation of MKP. Structure, 11, 155-164. PubMed id: 12575935 DOI: 10.1016/S0969-2126(02)00943-7
Date:
27-Jun-02     Release date:   27-Jun-03    
Supersedes: 1ikz
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q05923  (DUS2_HUMAN) -  Dual specificity protein phosphatase 2
Seq:
Struc:
314 a.a.
145 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class 1: E.C.3.1.3.16  - Protein-serine/threonine phosphatase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: [a protein]-serine/threonine phosphate + H2O = [a protein]- serine/threonine + phosphate
[a protein]-serine/threonine phosphate
+ H(2)O
= [a protein]- serine/threonine
+ phosphate
   Enzyme class 2: E.C.3.1.3.48  - Protein-tyrosine-phosphatase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Protein tyrosine phosphate + H2O = protein tyrosine + phosphate
Protein tyrosine phosphate
+ H(2)O
= protein tyrosine
+ phosphate
Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     dephosphorylation   2 terms 
  Biochemical function     phosphatase activity     3 terms  

 

 
    reference    
 
 
DOI no: 10.1016/S0969-2126(02)00943-7 Structure 11:155-164 (2003)
PubMed id: 12575935  
 
 
Solution structure of the MAPK phosphatase PAC-1 catalytic domain. Insights into substrate-induced enzymatic activation of MKP.
A.Farooq, O.Plotnikova, G.Chaturvedi, S.Yan, L.Zeng, Q.Zhang, M.M.Zhou.
 
  ABSTRACT  
 
Inactivation of mitogen-activated protein kinases (MAPKs) by MAPK phosphatases (MKPs) is accomplished via substrate-induced activation of the latter enzymes; however, the structural basis for the underlying mechanism remains elusive. Here, we report the three-dimensional solution structure of the C-terminal phosphatase domain of the prototypical MKP PAC-1, determined when bound to phosphate. Structural and biochemical analyses reveal unique active site geometry of the enzyme important for binding to phosphorylated threonine and tyrosine of MAPK ERK2. Our study further demonstrates that the dynamic interaction between the N-terminal kinase binding domain and the C-terminal phosphatase domain of an MKP is directly coupled to MAPK-induced conformational change of the phosphatase active site, which is essential for eliciting its full enzymatic activity.
 
  Selected figure(s)  
 
Figure 2.
Figure 2. NMR Structure of the Phosphatase Domain of PAC-1(A) Stereo view of the backbone atoms (N, C^a, and C') of 20 superimposed NMR-derived structures of the PAC-1 phosphatase domain (residues 170-314). Four N-terminal residues that are structurally disordered are omitted for clarity. The secondary-structural elements of a helices and b strands are colored in green and orange, respectively.(B) Ribbon depiction of the averaged minimized NMR structure of the phosphatase domain. Orientation of the structure and color-coding scheme for a helices and b strands in (A) and (B) are same.(C) Ribbon diagram of the PAC-1 structure in a view opposite to that shown in (B), illustrating the structural elements of the enzymatic active site (orange). Side chains of the active site residues D226, C257S, and R263 are color-coded by atom type.(D) Ribbon diagram of the crystal structure of the phosphatase domain of MKP-3, prepared with the structure coordinates obtained from the Protein Data Bank (ID code 1MKP). The orientation and color-coding for MKP-3 are similar to those used for PAC-1 in (C).(E and F) Electrostatic potential surface representation of the PAC-1 phosphatase domain. Negatively charged residues, red; positively charged residues, blue. The orientation of the molecular surface representation in (E) and (F) is similar to that in (B) and (C), respectively. (A) was prepared by InsightII, (B), (C), and (D) were prepared with Ribbons [41], and (E) and (F) were prepared by GRASP [42].
 
  The above figure is reprinted by permission from Cell Press: Structure (2003, 11, 155-164) copyright 2003.  
  Figure was selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
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.  
17596826 A.K.Nordle, P.Rios, A.Gaulton, R.Pulido, T.K.Attwood, and L.Tabernero (2007).
Functional assignment of MAPK phosphatase domains.
  Proteins, 69, 19-31.  
17078075 D.G.Jeong, Y.H.Cho, T.S.Yoon, J.H.Kim, S.E.Ryu, and S.J.Kim (2007).
Crystal structure of the catalytic domain of human DUSP5, a dual specificity MAP kinase protein phosphatase.
  Proteins, 66, 253-258.
PDB code: 2g6z
17313454 D.M.Arnold, C.Foster, D.M.Huryn, J.S.Lazo, P.A.Johnston, and P.Wipf (2007).
Synthesis and biological activity of a focused library of mitogen-activated protein kinase phosphatase inhibitors.
  Chem Biol Drug Des, 69, 23-30.  
17496916 D.M.Owens, and S.M.Keyse (2007).
Differential regulation of MAP kinase signalling by dual-specificity protein phosphatases.
  Oncogene, 26, 3203-3213.  
17505108 J.Phan, J.E.Tropea, and D.S.Waugh (2007).
Structure-assisted discovery of Variola major H1 phosphatase inhibitors.
  Acta Crystallogr D Biol Crystallogr, 63, 698-704.
PDB code: 2p4d
17473844 K.L.Jeffrey, M.Camps, C.Rommel, and C.R.Mackay (2007).
Targeting dual-specificity phosphatases: manipulating MAP kinase signalling and immune responses.
  Nat Rev Drug Discov, 6, 391-403.  
17044055 S.J.Kim, D.G.Jeong, T.S.Yoon, J.H.Son, S.K.Cho, S.E.Ryu, and J.H.Kim (2007).
Crystal structure of human TMDP, a testis-specific dual specificity protein phosphatase: implications for substrate specificity.
  Proteins, 66, 239-245.
PDB code: 2gwo
17400920 X.Tao, and L.Tong (2007).
Crystal structure of the MAP kinase binding domain and the catalytic domain of human MKP5.
  Protein Sci, 16, 880-886.
PDB codes: 2ouc 2oud
16474395 K.L.Jeffrey, T.Brummer, M.S.Rolph, S.M.Liu, N.A.Callejas, R.J.Grumont, C.Gillieron, F.Mackay, S.Grey, M.Camps, C.Rommel, S.D.Gerondakis, and C.R.Mackay (2006).
Positive regulation of immune cell function and inflammatory responses by phosphatase PAC-1.
  Nat Immunol, 7, 274-283.  
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.