PDBsum entry: 2p4d

Hydrolase

PDB id: 2p4d

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

Protein chain

P33064  (DUSP_VAR67) -  Dual specificity protein phosphatase H1

Seq: 171 a.a.

Struc: 163 a.a.

Enzyme reactions

• Enzyme class: E.C.3.1.3.48 - Protein-tyrosine-phosphatase.
• Reaction: Protein tyrosine phosphate + H₂O = protein tyrosine + phosphate

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 Gene Ontology (GO) functional annotation 

• Cellular component: virion (2 terms)
• Biological process: peptidyl-tyrosine dephosphorylation (5 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.