PDBsum entry: 1fpr

Signaling protein

PDB id: 1fpr

Contents

Protein chain

284 a.a. *

Ligands

GLU-ASP-THR-LEU-THR-PTR-ALA-ASP-LEU-ASP

* Residue conservation analysis

PDB id:

1fpr

Name:

Signaling protein

Title:

Crystal structure of the complex formed between the catalytic domain of shp-1 and an in vitro peptide substrate py469 derived from shps-1.

Structure:

Protein-tyrosine phosphatase 1c. Chain: a. Fragment: catalytic domain. Synonym: ptp-1c, hematopoietic cell protein-tyrosine phosphatase, sh-ptp1. Engineered: yes. Mutation: yes. Peptide py469. Chain: b.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Other_details: this peptide was chemically synthesized. The sequence of this peptide occurs naturally in humans (homo sapiens)

Biol. unit:

Tetramer (from PQS)

Resolution:

2.50Å R-factor: 0.194 R-free: 0.303

Authors:

J.Yang,Z.Cheng,Z.Niu,Z.J.Zhao,G.W.Zhou

Key ref:

J.Yang et al. (2000). Structural basis for substrate specificity of protein-tyrosine phosphatase SHP-1. J Biol Chem, 275, 4066-4071. PubMed id: 10660565 DOI: 10.1074/jbc.275.6.4066

Date:

31-Aug-00 Release date: 07-Mar-01

Protein chain

P29350  (PTN6_HUMAN) -  Tyrosine-protein phosphatase non-receptor type 6

Seq: 595 a.a.

Struc: 284 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: Protein tyrosine phosphate + H₂O = protein tyrosine + phosphate

Protein tyrosine phosphate (Bound ligand (Het Group name = PTR) matches with 76.00% similarity) + H(2)O = protein tyrosine + phosphate

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 (2 terms)

reference

DOI no: 10.1074/jbc.275.6.4066

J Biol Chem 275:4066-4071 (2000)

PubMed id: 10660565

Structural basis for substrate specificity of protein-tyrosine phosphatase SHP-1.

J.Yang, Z.Cheng, T.Niu, X.Liang, Z.J.Zhao, G.W.Zhou.

ABSTRACT

The substrate specificity of the catalytic domain of SHP-1, an important regulator in the proliferation and development of hematopoietic cells, is critical for understanding the physiological functions of SHP-1. Here we report the crystal structures of the catalytic domain of SHP-1 complexed with two peptide substrates derived from SIRPalpha, a member of the signal-regulatory proteins. We show that the variable beta5-loop-beta6 motif confers SHP-1 substrate specificity at the P-4 and further N-terminal subpockets. We also observe a novel residue shift at P-2, the highly conserved subpocket in protein- tyrosine phosphatases. Our observations provide new insight into the substrate specificity of SHP-1.

Selected figure(s)

Figure 1.
Fig. 1. A and B, the electron density maps (2F[o] F[c]) for the phosphotyrosyl peptide sites in both Tyr(P)469 (A) and Tyr(P)495 (B) complexes. The maps are contoured at 1.0 to 2.5 (A) and 2.3 Å (B), respectively, with the refined models of the decapeptides in yellow. The amino acids are labeled. C and D, ribbon representations of the Tyr(P)469 (C) and the Tyr(P)495 (D) complex structures. The peptides are shown in the stick model. The catalytic domain of SHP-1 is shown in green. Structures of the catalytic domain in the two complexes were almost identical, with an r.m.s deviation of 0.5 Å. They were also similar to the native catalytic domain structure (7), with an r.m.s deviation of 0.8 Å. This Fig. was prepared by SETOR (25). E, comparison of peptides Tyr(P)469 and Tyr(P)495 after superimposing two complexes on their catalytic domains. Peptides Tyr(P)469 and Tyr(P)495 are shown in yellow and blue, respectively.

Figure 3.
Fig. 3. Superimposition of the Tyr(P)469 and Tyr(P)495 complex structures with the PTP1B-hexapeptide complex structure. The peptides are shown as stick models, and the catalytic domains are shown as ribbons. The Tyr(P)469, Tyr(P)495, and PTP1B complex structures are shown in yellow, blue, and gray, respectively. The only similarity between the SHP-1-peptide complex structures and PTP1B-hexapeptide structure was that residue Tyr(P) fit into the Tyr(P)-binding subpocket, and the phosphate group of residue Tyr(P) made extensive hydrogen bonds with the PTP signature motif. In the PTP1B-hexapeptide structure, the side chain of residue Leu P+1 pointed in the direction of the main chain of peptides Tyr(P)469 and Tyr(P)495 in the SHP-1 complex structures. This directional change may have been caused by the end effects (i.e. LeuP+1 is the C-terminal residue). However, at the N terminus the peptide was positioned away from the PTP1B molecule and extended into the solvent.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2000, 275, 4066-4071) copyright 2000.

Figures were selected by the author.