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PDBsum entry 1zzw

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protein ligands Protein-protein interface(s) links
Hydrolase PDB id
1zzw
Jmol
Contents
Protein chain
147 a.a. *
Ligands
SO4 ×2
EDO
Waters ×263
* Residue conservation analysis
PDB id:
1zzw
Name: Hydrolase
Title: Crystal structure of catalytic domain of human map kinase phosphatase 5
Structure: Dual specificity protein phosphatase 10. Chain: a, b. Fragment: catalytic domain. Synonym: mitogen-activated protein kinase phosphatase 5, map kinase phosphatase 5, mkp-5. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Resolution:
1.60Å     R-factor:   0.193     R-free:   0.217
Authors: D.G.Jeong,T.S.Yoon,J.H.Kim,M.Y.Shim,S.K.Jeong,J.H.Son, S.E.Ryu,S.J.Kim
Key ref:
D.G.Jeong et al. (2006). Crystal structure of the catalytic domain of human MAP kinase phosphatase 5: structural insight into constitutively active phosphatase. J Mol Biol, 360, 946-955. PubMed id: 16806267 DOI: 10.1016/j.jmb.2006.05.059
Date:
14-Jun-05     Release date:   04-Jul-06    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q9Y6W6  (DUS10_HUMAN) -  Dual specificity protein phosphatase 10
Seq:
Struc:
482 a.a.
147 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     4 terms  

 

 
    reference    
 
 
DOI no: 10.1016/j.jmb.2006.05.059 J Mol Biol 360:946-955 (2006)
PubMed id: 16806267  
 
 
Crystal structure of the catalytic domain of human MAP kinase phosphatase 5: structural insight into constitutively active phosphatase.
D.G.Jeong, T.S.Yoon, J.H.Kim, M.Y.Shim, S.K.Jung, J.H.Son, S.E.Ryu, S.J.Kim.
 
  ABSTRACT  
 
MAP kinase phosphatase 5 (MKP5) is a member of the mitogen-activated protein kinase phosphatase (MKP) family and selectively dephosphorylates JNK and p38. We have determined the crystal structure of the catalytic domain of human MKP5 (MKP5-C) to 1.6 A. In previously reported MKP-C structures, the residues that constitute the active site are seriously deviated from the active conformation of protein tyrosine phosphatases (PTPs), which are accompanied by low catalytic activity. High activities of MKPs are achieved by binding their cognate substrates, representing substrate-induced activation. However, the MKP5-C structure adopts an active conformation of PTP even in the absence of its substrate binding, which is consistent with the previous results that MKP5 solely possesses the intrinsic activity. Further, we identify a sequence motif common to the members of MKPs having low catalytic activity by comparing structures and sequences of other MKPs. Our structural information provides an explanation of constitutive activity of MKP5 as well as the structural insight into substrate-induced activation occurred in other MKPs.
 
  Selected figure(s)  
 
Figure 2.
Figure 2. (a) Cα trace. The Cα trace of the MKP5-C structure (thick line) is superimposed with that of the MKP3 structure (thin line). The regions of MKP5-C that cannot be aligned are colored green whereas the corresponding regions of MKP3 are colored red. The secondary structural elements are indicated. The point of view is the same as in Figure 1(a). (b) Comparison with MKP3. The active sites of MKP5-C (orange) and MKP3-C (grey) were superposed and presented as worm models. MKP5-C residues are labeled in black whereas MKP3-C residues (cyan) are labeled in red.
Figure 4.
Figure 4. (a) The superposition of the PTP loop, general acid loop and β3–β4 loop of MKP5-C (orange) with the equivalent regions of MKP3-C (grey). Selected side-chains of MKP5-C and MKP3-C are shown and labeled black and red, respectively. The hydrogen bond is represented as a dotted line. MKB is bound to the one side of inactive MKP-C, which include strand β3′, helices α2 and α5. The active structure is adapted from MKP5-C whereas the inactive one is from MKP3-C (PDB code: 1MKP). The regions that contributed to the binding to MKB are colored red. The PTP loop including its surrounding loops that adopt an active conformation are colored cyan whereas those that adopt an inactive one are in orange. (b) A hypothetical model of the substrate-induced activation by conformational rearrangement. MAPK binding to MKB allosterically induces a conformational transition of MKP-C from the β3′ strand to the β3–β4 loop. The transition may disrupt the interactions that stabilize the inactive conformation of MKP-C, which concomitantly lead to an active conformation.
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2006, 360, 946-955) copyright 2006.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
19415758 D.G.Jeong, S.K.Jung, T.S.Yoon, E.J.Woo, J.H.Kim, B.C.Park, S.E.Ryu, and S.J.Kim (2009).
Crystal structure of the catalytic domain of human MKP-2 reveals a 24-mer assembly.
  Proteins, 76, 763-767.
PDB code: 3ezz
19578332 G.Molina, A.Vogt, A.Bakan, W.Dai, P.Queiroz de Oliveira, W.Znosko, T.E.Smithgall, I.Bahar, J.S.Lazo, B.W.Day, and M.Tsang (2009).
Zebrafish chemical screening reveals an inhibitor of Dusp6 that expands cardiac cell lineages.
  Nat Chem Biol, 5, 680-687.  
19770498 G.T.Lountos, J.E.Tropea, S.Cherry, and D.S.Waugh (2009).
Overproduction, purification and structure determination of human dual-specificity phosphatase 14.
  Acta Crystallogr D Biol Crystallogr, 65, 1013-1020.
PDB code: 2wgp
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.  
18298792 R.Pulido, and R.Hooft van Huijsduijnen (2008).
Protein tyrosine phosphatases: dual-specificity phosphatases in health and disease.
  FEBS J, 275, 848-866.  
17303404 C.R.Weston, and R.J.Davis (2007).
The JNK signal transduction pathway.
  Curr Opin Cell Biol, 19, 142-149.  
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
17427953 S.K.Jung, D.G.Jeong, T.S.Yoon, J.H.Kim, S.E.Ryu, and S.J.Kim (2007).
Crystal structure of human slingshot phosphatase 2.
  Proteins, 68, 408-412.
PDB code: 2nt2
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
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.