PDBsum entry: 1hzm

Hydrolase

PDB id: 1hzm

Contents

Protein chain

154 a.a. *

* Residue conservation analysis

PDB id:

1hzm

Name:

Hydrolase

Title:

Structure of erk2 binding domain of mapk phosphatase mkp-3: structural insights into mkp-3 activation by erk2

Structure:

Dual specificity protein phosphatase 6. Chain: a. Fragment: residues 1-154. Synonym: mitogen-activated protein kinase phosphatase 3. Map kinase phosphatase 3. Mkp-3. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

NMR struc:

1 models

Authors:

A.Farooq,M.-M.Zhou

Key ref:

A.Farooq et al. (2001). Solution structure of ERK2 binding domain of MAPK phosphatase MKP-3: structural insights into MKP-3 activation by ERK2. Mol Cell, 7, 387-399. PubMed id: 11239467 DOI: 10.1016/S1097-2765(01)00186-1

Date:

25-Jan-01 Release date: 25-Jan-02

Protein chain

Q16828  (DUS6_HUMAN) -  Dual specificity protein phosphatase 6

Seq: 381 a.a.

Struc: 154 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: protein dephosphorylation (1 term)
• Biochemical function: protein tyrosine/serine/threonine phosphatase activity (1 term)

reference

DOI no: 10.1016/S1097-2765(01)00186-1

Mol Cell 7:387-399 (2001)

PubMed id: 11239467

Solution structure of ERK2 binding domain of MAPK phosphatase MKP-3: structural insights into MKP-3 activation by ERK2.

A.Farooq, G.Chaturvedi, S.Mujtaba, O.Plotnikova, L.Zeng, C.Dhalluin, R.Ashton, M.M.Zhou.

ABSTRACT

MAP kinases (MAPKs), which control mitogenic signal transduction in all eukaryotic organisms, are inactivated by dual specificity MAPK phosphatases (MKPs). MKP-3, a prototypical MKP, achieves substrate specificity through its N-terminal domain binding to the MAPK ERK2, resulting in the activation of its C-terminal phosphatase domain. The solution structure and biochemical analysis of the ERK2 binding (EB) domain of MKP-3 show that regions that are essential for ERK2 binding partly overlap with its sites that interact with the C-terminal catalytic domain, and that these interactions are functionally coupled to the active site residues of MKP-3. Our findings suggest a novel mechanism by which the EB domain binding to ERK2 is transduced to cause a conformational change of the C-terminal catalytic domain, resulting in the enzymatic activation of MKP-3.

Selected figure(s)

Figure 2.
Figure 2. Overview of the MKP-3 EB Domain Structure(A) Stereoview of the backbone atoms (N, C^α, and C′) of 20 superimposed NMR-derived structures of the MKP-3 EB domain (residues 10–152). The terminal residues, which are structurally disordered, are omitted for clarity. The secondary structural elements of α helices and β strands are colored in green and orange, respectively. These figures were produced using InsightII.(B) Ribbon depiction of the averaged minimized NMR structure of the EB domain. The orientation of the protein structure in (B) is as shown in (A). The color-coding scheme for α helices and β strands is the same as that used in (A).(C) Ribbon diagram of the EB domain structure, rotated vert, similar 90° from the orientation in (B) as indicated in the figure. These figures were prepared using Ribbons (Carson, 1991)

Figure 5.
Figure 5. Electrostatic Potential Surface Representations of the MKP-3 EB Domain and ERK2(A) Electrostatic potential map of the MKP-3 EB domain. Negatively and positively charged residues are shown in red and blue, respectively. Orientation of the molecular surface representation is shown in Figure 3C, rotated clockwise by vert, similar 60° about the vertical axis. Numerals indicate specific amino acid residues of the protein.(B) Electrostatic potential map of ERK2. Negatively and positively charged residues are shown in red and blue, respectively. Numerals indicate locations of functionally important amino acid residues of the protein, including D319 as well as T183 and Y185 in the activation loop

The above figures are reprinted by permission from Cell Press: Mol Cell (2001, 7, 387-399) copyright 2001.

Figures were selected by an automated process.