PDBsum entry: 1c25

Hydrolase

PDB-id: 1c25

Contents

Description

Header details

Header records

References

PROCHECK

Protein chain

161 a.a. *

Waters ×82

* Residue conservation analysis

Tools

Clefts Calculation

PDB id:

1c25

Name:

Hydrolase

Title:

Human cdc25a catalytic domain

Structure:

Cdc25a. Chain: a. Fragment: catalytic domain. Synonym: m-phase inducer phosphatase 1. Engineered: yes. Mutation: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Cell_line: bl21. Cellular_location: cytoplasm. Gene: cdc25a. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

UniProt:

P30304 (MPIP1_HUMAN)

Seq:

Struc:

Seq:

Struc:

Seq:

524 a.a.

Struc:

161 a.a.*

Key:	PfamA domain
Secondary structure	CATH domain

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme class:

E.C.3.1.3.48   [IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

Reaction:

Protein tyrosine phosphate + H₂O = protein tyrosine + phosphate (see diagram below)

Resolution:

2.30Å

R-factor:

0.227

R-free:

0.296

Authors:

E.B.Fauman,J.P.Cogswell,B.Lovejoy,W.J.Rocque,W.Holmes, V.G.Montana,H.Piwnica-Worms,M.J.Rink,M.A.Saper

Key ref:

E.B.Fauman et al. (1998). Crystal structure of the catalytic domain of the human cell cycle control phosphatase, Cdc25A.. Cell, 93, 617-625. [PubMed id: 9604936] [DOI: 10.1016/S0092-8674(00)81190-3]

Date:

17-Apr-98

Release date:

19-Aug-98

Quick_links

Procheck

Clefts

Surface

Key reference

DOI no: 10.1016/S0092-8674(00)81190-3

Cell 93:617-625 (1998)

PubMed id: 9604936

Crystal structure of the catalytic domain of the human cell cycle control phosphatase, Cdc25A.

E.B.Fauman, J.P.Cogswell, B.Lovejoy, W.J.Rocque, W.Holmes, V.G.Montana, H.Piwnica-Worms, M.J.Rink, M.A.Saper.

ABSTRACT

Cdc25 phosphatases activate the cell division kinases throughout the cell cycle. The 2.3 A structure of the human Cdc25A catalytic domain reveals a small alpha/beta domain with a fold unlike previously described phosphatase structures but identical to rhodanese, a sulfur-transfer protein. Only the active-site loop, containing the Cys-(X)5-Arg motif, shows similarity to the tyrosine phosphatases. In some crystals, the catalytic Cys-430 forms a disulfide bond with the invariant Cys-384, suggesting that Cdc25 may be self-inhibited during oxidative stress. Asp-383, previously proposed to be the general acid, instead serves a structural role, forming a conserved buried salt-bridge. We propose that Glu-431 may act as a general acid. Structure-based alignments suggest that the noncatalytic domain of the MAP kinase phosphatases will share this topology, as will ACR2, a eukaryotic arsenical resistance protein.

Selected figure(s)

Figure 2.
Figure 2. Ribbon Drawing of the Catalytic Domain of Human Cdc25AThe CH2A, active site, and CH2B motifs are indicated in green, red, and blue, respectively. The side chain of the Cys-430 nucleophile is shown in yellow. The N terminus (residue 335) is indicated on the left (N), while the C terminus extends toward the viewer and is clipped in this figure. Figure created with MOLSCRIPT ([31]) and the ray-tracing program VORT (University of Melbourne).

Figure 5.
Figure 5. The Active Site of Cdc25A(A) Ball-and-stick model.(B) CPK model, in the same orientation, with a molecular surface ([37]) in gold. Unlabeled residues are gray; all others are colored according to chemical property. The C-terminal tail of Cdc25A can be seen behind the active site, extending away from the protein. Graphics rendered with O ( [29]) and VORT (University of Melbourne).

The above figures are reprinted by permission from Cell Press: Cell (1998, 93, 617-625) copyright 1998.

Figures were selected by the author.