PDBsum entry: 1m3g

Hydrolase

PDB id: 1m3g

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

Protein chain

Q05923  (DUS2_HUMAN) -  Dual specificity protein phosphatase 2

Seq: 314 a.a.

Struc: 145 a.a.*

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

Enzyme reactions

• Enzyme class 1: E.C.3.1.3.16 - Phosphoprotein phosphatase.
• Reaction: A phosphoprotein + H₂O = a protein + phosphate
• Enzyme class 2: E.C.3.1.3.48 - Protein-tyrosine-phosphatase.
• Reaction: Protein tyrosine phosphate + H₂O = 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 

• 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.