PDBsum entry 2shp

Tyrosine phosphatase

PDB id: 2shp

Contents

Protein chain

491 a.a. *

Ligands

CAT ×2

Waters ×2331

* Residue conservation analysis

PDB id:

2shp

Name:

Tyrosine phosphatase

Title:

Tyrosine phosphatase shp-2

Structure:

Shp-2. Chain: a, b. Synonym: syp, shptp-2. Engineered: yes. Mutation: yes

Source:

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

Resolution:

2.00Å R-factor: 0.199 R-free: 0.270

Authors:

P.Hof,S.Pluskey,S.Dhe-Paganon,M.J.Eck,S.E.Shoelson

Key ref:

P.Hof et al. (1998). Crystal structure of the tyrosine phosphatase SHP-2. Cell, 92, 441-450. PubMed id: 9491886 DOI: 10.1016/S0092-8674(00)80938-1

Date:

01-Dec-97 Release date: 16-Feb-99

Protein chains

Q06124  (PTN11_HUMAN) -  Tyrosine-protein phosphatase non-receptor type 11 from Homo sapiens

Seq: 593 a.a.

Struc: 491 a.a.*

* PDB and UniProt seqs differ at 3 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.3.1.3.48 - protein-tyrosine-phosphatase.
• Reaction: O-phospho-L-tyrosyl-[protein] + H2O = L-tyrosyl-[protein] + phosphate

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

Key reference

DOI no: 10.1016/S0092-8674(00)80938-1

Cell 92:441-450 (1998)

PubMed id: 9491886

Crystal structure of the tyrosine phosphatase SHP-2.

P.Hof, S.Pluskey, S.Dhe-Paganon, M.J.Eck, S.E.Shoelson.

ABSTRACT

The structure of the SHP-2 tyrosine phosphatase, determined at 2.0 angstroms resolution, shows how its catalytic activity is regulated by its two SH2 domains. In the absence of a tyrosine-phosphorylated binding partner, the N-terminal SH2 domain binds the phosphatase domain and directly blocks its active site. This interaction alters the structure of the N-SH2 domain, disrupting its phosphopeptide-binding cleft. Conversely, interaction of the N-SH2 domain with phosphopeptide disrupts its phosphatase recognition surface. Thus, the N-SH2 domain is a conformational switch; it either binds and inhibits the phosphatase, or it binds phosphoproteins and activates the enzyme. Recognition of bisphosphorylated ligands by the tandem SH2 domains is an integral element of this switch; the C-terminal SH2 domain contributes binding energy and specificity, but it does not have a direct role in activation.

Selected figure(s)

Figure 2.
Figure 2. The Structure of SHP-2 in Its Autoinhibited, Closed ConfigurationStructures in (A) and (B) are in similar orientations. The N- and C-terminal SH2 domains are yellow and green, respectively; the catalytic PTP domain is blue, and interdomain linkers (residues 104–111 and 217–220) are white in both panels.(A) Richardson diagram showing secondary structure and organization of the domains. Orange, the side chain of Cys459 (the catalytic nucleophile); dashed lines, disordered loops.(B) All nonhydrogen atoms of SHP-2 are displayed. Although SH2 domain–bound peptides are not present in our structure, residues of both domains known to contact phosphopeptides ([32]; [15]) are colored red. Note that peptide binding sites of both SH2 domains are exposed on the molecule surface. A distinct surface of the N-SH2 domain occupies the active site of the PTP domain. Magenta, residues of the PTP signature motif, HCSAGIGRS; these residues participate in catalysis and phosphate binding.

Figure 6.
Figure 6. A Conformational Change in the N-SH2 Domain Regulates SHP-2(A) An α-carbon trace of the phosphopeptide-bound A conformation of the N-SH2 domain (red) ([15]) is superimposed on the I state domain in the present structure (yellow). The domains were superimposed using the invariant portions of the structure (residues 6–55) as determined by analysis of difference distance matrix plots with the program DDMP ( [44]). The molecular surface of the PTP and C-SH2 domains is shown in blue. Note that in the peptide-bound A state, the N-SH2 backbone (red) would collide with the surface of the PTP domain.(B) Molecular surfaces of the N-SH2 domain from the SHP-2 structure (I state) and the isolated SH2 domain bound to a phosphopeptide (A state) ([32]); the domains are oriented similarly according to elements of secondary structure. Residues of the EF (66–68) and BG (89–92) loops are green and red, respectively. A stick figure with carbon colored white, the PDGFR 1009 peptide; blue, nitrogen; red, oxygen; yellow, phosphorus. Closure of the EF and BG loops in the I state precludes high-affinity phosphopeptide binding. The change in shape of the N-SH2 domain that accompanies phosphopeptide binding destroys surface complementarity for the PTP active site. Phosphopeptide binding thus promotes dissociation of the N-SH2 and PTP domains to generate the active A state of SHP-2.

The above figures are reprinted by permission from Cell Press: Cell (1998, 92, 441-450) copyright 1998.

Figures were selected by the author.