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PDBsum entry 2p4d

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protein links
Hydrolase PDB id
2p4d
Jmol
Contents
Protein chain
163 a.a. *
Waters ×190
* Residue conservation analysis
PDB id:
2p4d
Name: Hydrolase
Title: Structure-assisted discovery of variola major h1 phosphatase inhibitors
Structure: Dual specificity protein phosphatase. Chain: a. Fragment: enzyme. Synonym: late protein h1. Engineered: yes
Source: Variola virus. Organism_taxid: 10255. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Resolution:
1.80Å     R-factor:   0.179     R-free:   0.195
Authors: J.Phan,J.E.Tropea,D.S.Waugh
Key ref:
J.Phan et al. (2007). Structure-assisted discovery of Variola major H1 phosphatase inhibitors. Acta Crystallogr D Biol Crystallogr, 63, 698-704. PubMed id: 17505108 DOI: 10.1107/S0907444907014904
Date:
12-Mar-07     Release date:   29-May-07    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P33064  (DUSP_VAR67) -  Dual specificity protein phosphatase H1
Seq:
Struc:
171 a.a.
163 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: 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
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     virion   2 terms 
  Biological process     viral reproduction   8 terms 
  Biochemical function     hydrolase activity     5 terms  

 

 
    reference    
 
 
DOI no: 10.1107/S0907444907014904 Acta Crystallogr D Biol Crystallogr 63:698-704 (2007)
PubMed id: 17505108  
 
 
Structure-assisted discovery of Variola major H1 phosphatase inhibitors.
J.Phan, J.E.Tropea, D.S.Waugh.
 
  ABSTRACT  
 
Variola major virus, the causative agent of smallpox, encodes the dual-specificity H1 phosphatase. Because this enzyme is essential for the production of mature virus particles, it is an attractive molecular target for the development of therapeutic countermeasures for this potential agent of bioterrorism. As a first step in this direction, the crystal structure of H1 phosphatase has been determined at a resolution of 1.8 A. In silico screening methods have led to the identification of several small molecules that inhibit Variola H1 phosphatase with IC(50) values in the low micromolar range. These molecules provide novel leads for future drug development.
 
  Selected figure(s)  
 
Figure 1.
Figure 1 Ribbon model of the V. major H1 phosphatase shown with a rainbow coloring scheme. The enzyme crystallized as a domain-swapped dimer. The N- and C-termini of the two subunits are labeled in blue and green. The catalytic residue Cys110 is highlighted in bond and CPK format. Figs. 1-and 2-were prepared using the programs MOLSCRIPT (Kraulis, 1991[Kraulis, P. J. (1991). J. Appl. Cryst. 24, 946-950.]) and RASTER3D (Merritt & Murphy, 1994[Merritt, E. A. & Murphy, M. E. P. (1994). Acta Cryst. D50, 869-873.]).
Figure 2.
Figure 2 Comparison of Variola H1 phosphatase with human VHR phosphatase. The ribbon model of the VHR monomer (magenta) is superimposed on a subunit of the H1 dimer (blue and green). The N-terminal helix of VHR has a similar conformation to that of the swapped molecule (green). The catalytic Cys110 of H1 is shown in ball-and-stick representation.
 
  The above figures are reprinted by permission from the IUCr: Acta Crystallogr D Biol Crystallogr (2007, 63, 698-704) copyright 2007.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21543850 G.T.Lountos, J.E.Tropea, and D.S.Waugh (2011).
Structure of human dual-specificity phosphatase 27 at 2.38 Å resolution.
  Acta Crystallogr D Biol Crystallogr, 67, 471-479.
PDB code: 2y96
19211553 A.C.Koksal, J.D.Nardozzi, and G.Cingolani (2009).
Dimeric quaternary structure of the prototypical dual specificity phosphatase VH1.
  J Biol Chem, 284, 10129-10137.
PDB code: 3cm3
19946139 K.Van Vliet, M.R.Mohamed, L.Zhang, N.Y.Villa, S.J.Werden, J.Liu, and G.McFadden (2009).
Poxvirus proteomics and virus-host protein interactions.
  Microbiol Mol Biol Rev, 73, 730-749.  
  18323605 L.Roces, P.P.Knowles, G.Fox, J.Juanhuix, N.Scaplehorn, M.Way, and N.Q.McDonald (2008).
Crystallization and preliminary X-ray diffraction analysis of vaccinia virus H1L phosphatase.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 64, 190-192.  
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.