PDBsum entry 1g1f

Hydrolase, signaling protein

PDB id: 1g1f

Contents

Protein chain

297 a.a. *

Ligands

GLU-THR-ASP-PTR-PTR-ARG

Waters ×247

* Residue conservation analysis

PDB id:

1g1f

Name:

Hydrolase, signaling protein

Title:

Crystal structure of protein tyrosine phosphatase 1b complexed with a tri-phosphorylated peptide (rdi(ptr)etd(ptr)(ptr)rk) from the insulin receptor kinase

Structure:

Protein tyrosine phosphatase 1b. Chain: a. Fragment: catalytic domain. Synonym: ptp1b, protein tyrosine phosphatase, non-receptor type 1. Engineered: yes. Mutation: yes. Tri-phosphorylated peptide from the insulin receptor kinase. Chain: b.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Other_details: sequence from the activation segment of the insulin recptor kinase

Biol. unit:

Dimer (from PQS)

Resolution:

2.00Å R-factor: 0.207 R-free: 0.227

Authors:

A.Salmeen,J.N.Andersen,M.P.Myers,N.K.Tonks,D.Barford

Key ref:

A.Salmeen et al. (2000). Molecular basis for the dephosphorylation of the activation segment of the insulin receptor by protein tyrosine phosphatase 1B. Mol Cell, 6, 1401-1412. PubMed id: 11163213 DOI: 10.1016/S1097-2765(00)00137-4

Date:

11-Oct-00 Release date: 17-Jan-01

Protein chain

P18031  (PTN1_HUMAN) -  Tyrosine-protein phosphatase non-receptor type 1 from Homo sapiens

Seq: 435 a.a.

Struc: 297 a.a.*

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

Enzyme reactions

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

O-phospho-L-tyrosyl-[protein] (Bound ligand (Het Group name = PTR) matches with 76.19% similarity) + H2O = L-tyrosyl-[protein] + phosphate

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

Key reference

DOI no: 10.1016/S1097-2765(00)00137-4

Mol Cell 6:1401-1412 (2000)

PubMed id: 11163213

Molecular basis for the dephosphorylation of the activation segment of the insulin receptor by protein tyrosine phosphatase 1B.

A.Salmeen, J.N.Andersen, M.P.Myers, N.K.Tonks, D.Barford.

ABSTRACT

The protein tyrosine phosphatase PTP1B is responsible for negatively regulating insulin signaling by dephosphorylating the phosphotyrosine residues of the insulin receptor kinase (IRK) activation segment. Here, by integrating crystallographic, kinetic, and PTP1B peptide binding studies, we define the molecular specificity of this reaction. Extensive interactions are formed between PTP1B and the IRK sequence encompassing the tandem pTyr residues at 1162 and 1163 such that pTyr-1162 is selected at the catalytic site and pTyr-1163 is located within an adjacent pTyr recognition site. This selectivity is attributed to the 70-fold greater affinity for tandem pTyr-containing peptides relative to mono-pTyr peptides and predicts a hierarchical dephosphorylation process. Many elements of the PTP1B-IRK interaction are unique to PTP1B, indicating that it may be feasible to generate specific, small molecule inhibitors of this interaction to treat diabetes and obesity.

Selected figure(s)

Figure 2.
Figure 2. Structure of the PTP1B Bisphosphorylated IR Peptide Complex(A) Overview. The PTP loop (residues 215–222) of PTP1B is shown in yellow, the WPD loop (residues 179-185) in maroon, the pTyr loop (residues 45–49) in purple, and the Q loop (residues 258–262) in pink.(B) Stereo view showing details of the interactions between the bisphosphorylated IRK peptide and PTP1B.(C) 2F[o]-F[c] electron density omit map, contoured at the 1 σ level, for the IRK peptide; only pTyr-1162 was included in the refinement and phase calculation of the map.

Figure 5.
Figure 5. Schematic Representation of the PTP1B Bisphosphorylated IR Peptide Interactions

The above figures are reprinted by permission from Cell Press: Mol Cell (2000, 6, 1401-1412) copyright 2000.

Figures were selected by an automated process.