PDBsum entry 2ouc

Hydrolase

PDB id: 2ouc

Contents

Protein chains

132 a.a. *

Waters ×115

* Residue conservation analysis

PDB id:

2ouc

Name:

Hydrolase

Title:

Crystal structure of the map kinase binding domain of mkp5

Structure:

Dual specificity protein phosphatase 10. Chain: a, b. Fragment: rhodanese domain (residues 148-287). Synonym: mitogen-activated protein kinase phosphatase 5, map kinase phosphatase 5, mkp-5. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: mkp5. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

2.20Å R-factor: 0.232 R-free: 0.289

Authors:

X.Tao,L.Tong

Key ref:

X.Tao and L.Tong (2007). Crystal structure of the MAP kinase binding domain and the catalytic domain of human MKP5. Protein Sci, 16, 880-886. PubMed id: 17400920 DOI: 10.1110/ps.062712807

Date:

10-Feb-07 Release date: 07-Aug-07

Protein chains

Q9Y6W6  (DUS10_HUMAN) -  Dual specificity protein phosphatase 10 from Homo sapiens

Seq: 482 a.a.

Struc: 132 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

Enzyme reactions

• Enzyme class 1: E.C.3.1.3.16 - protein-serine/threonine phosphatase.
• Reaction:
  1. O-phospho-L-seryl-[protein] + H2O = L-seryl-[protein] + phosphate
  2. O-phospho-L-threonyl-[protein] + H2O = L-threonyl-[protein] + phosphate
• Enzyme class 2: E.C.3.1.3.48 - protein-tyrosine-phosphatase.
• Reaction: O-phospho-L-tyrosyl-[protein] + H2O = L-tyrosyl-[protein] + 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

reference

DOI no: 10.1110/ps.062712807

Protein Sci 16:880-886 (2007)

PubMed id: 17400920

Crystal structure of the MAP kinase binding domain and the catalytic domain of human MKP5.

X.Tao, L.Tong.

ABSTRACT

MAP kinase phosphatases (MKPs) have crucial roles in regulating the signaling activity of MAP kinases and are potential targets for drug discovery against human diseases. These enzymes contain a catalytic domain (CD) as well as a binding domain (BD) that help recognize the target MAP kinase. We report here the crystal structures at up to 2.2 A resolution of the BD and CD of human MKP5 and compare them to the known structures from other MKPs. Dramatic structural differences are observed between the BD of MKP5 and that of MKP3 determined previously by NMR. In particular, the cluster of positively charged residues that is important for MAP kinase binding is located in completely different positions in the two structures, with a distance of 25 A between them. Moreover, this cluster is alpha-helical in MKP5, while it forms a loop followed by a beta-strand in MKP3. These large structural differences could be associated with the distinct substrate preferences of these phosphatases, but further studies are needed to confirm this. The CD of MKP5 is observed in an active conformation, and two loops in the active site have backbone shifts of up to 5 A relative to the inactive CDs from other MKPs.

Selected figure(s)

Figure 2.
Figure 2. Structure of the MAP kinase binding domain of MKP5. (A) Schematic representation of the structure of the binding domain

Figure 5.
Figure 5. Structural comparison between the catalytic domains of MKP5

The above figures are reprinted by permission from the Protein Society: Protein Sci (2007, 16, 880-886) copyright 2007.

Figures were selected by an automated process.