PDBsum entry 2b4s

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protein ligands Protein-protein interface(s) links
Hydrolase/transferase PDB id
Protein chains
289 a.a. *
297 a.a. *
SO4 ×10
Waters ×377
* Residue conservation analysis
PDB id:
Name: Hydrolase/transferase
Title: Crystal structure of a complex between ptp1b and the insulin receptor tyrosine kinase
Structure: Tyrosine-protein phosphatase, non-receptor type 1. Chain: a, c. Synonym: protein-tyrosine phosphatase 1b, ptp-1b. Engineered: yes. Insulin receptor. Chain: b, d. Fragment: protein kinase. Synonym: ir, cd220 antigen.
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: ptpn1, ptp1b. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Gene: insr. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108.
Biol. unit: Tetramer (from PQS)
2.30Å     R-factor:   0.208     R-free:   0.239
Authors: S.Li,R.S.Depetris,D.Barford,J.Chernoff,S.R.Hubbard
Key ref:
S.Li et al. (2005). Crystal structure of a complex between protein tyrosine phosphatase 1B and the insulin receptor tyrosine kinase. Structure (Camb), 13, 1643-1651. PubMed id: 16271887 DOI: 10.1016/j.str.2005.07.019
26-Sep-05     Release date:   15-Nov-05    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P18031  (PTN1_HUMAN) -  Tyrosine-protein phosphatase non-receptor type 1
435 a.a.
289 a.a.*
Protein chains
Pfam   ArchSchema ?
P06213  (INSR_HUMAN) -  Insulin receptor
1382 a.a.
297 a.a.*
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class 1: Chains A, C: E.C.  - Protein-tyrosine-phosphatase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Protein tyrosine phosphate + H2O = protein tyrosine + phosphate
Protein tyrosine phosphate
+ H(2)O
= protein tyrosine
+ phosphate
   Enzyme class 2: Chains B, D: E.C.  - Receptor protein-tyrosine kinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate
+ [protein]-L-tyrosine
+ [protein]-L-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 
  GO annot!
  Cellular component     membrane   1 term 
  Biological process     dephosphorylation   4 terms 
  Biochemical function     transferase activity, transferring phosphorus-containing groups     7 terms  


DOI no: 10.1016/j.str.2005.07.019 Structure (Camb) 13:1643-1651 (2005)
PubMed id: 16271887  
Crystal structure of a complex between protein tyrosine phosphatase 1B and the insulin receptor tyrosine kinase.
S.Li, R.S.Depetris, D.Barford, J.Chernoff, S.R.Hubbard.
Protein tyrosine phosphatase 1B (PTP1B) is a highly specific negative regulator of insulin receptor signaling in vivo. The determinants of PTP1B specificity for the insulin receptor versus other receptor tyrosine kinases are largely unknown. Here, we report a crystal structure at 2.3 A resolution of the catalytic domain of PTP1B (trapping mutant) in complex with the phosphorylated tyrosine kinase domain of the insulin receptor (IRK). The crystallographic asymmetric unit contains two PTP1B-IRK complexes that interact through an IRK dimer interface. Rather than binding to a phosphotyrosine in the IRK activation loop, PTP1B binds instead to the opposite side of the kinase domain, with the phosphorylated activation loops sequestered within the IRK dimer. The crystal structure provides evidence for a noncatalytic mode of interaction between PTP1B and IRK, which could be important for the selective recruitment of PTP1B to the insulin receptor.
  Selected figure(s)  
Figure 3.
Figure 3. Superposition of PTP1B Structures
(A) The Ca trace of PTP1B from the PTP1B-IRK complex is colored cyan, and the superimposed Ca trace from the PTP1B-phosphopeptide structure (Salmeen et al., 2000) (PDB code 1G1F) is colored orange. The WPD loop (residues 179-184) in each PTP1B structure is colored gray, and the catalytic loop (residues 215-218) is colored red. The b2-b3 loop of IRK from the PTP1B-IRK structure is colored yellow, and the IRK phosphopeptide from the 1G1F structure is colored magenta. Select secondary structure elements are labeled, and the N and C termini of the two PTP1B structures are denoted by "N" and "C," respectively. The first ordered residue in both structures is E2, while the last ordered residue is M282 in the PTP1B-IRK structure and D298 in the 1G1F structure. Where termini or secondary structure elements overlap between the two PTP1B structures, the labels are colored black, otherwise they are colored cyan (PTP1B-IRK) or orange (1G1F). The black rectangle indicates the zoom area in (B).
(B) Stereoview near the active site of PTP1B. Select side chains of the two PTP1B structures, as well as the sulfate ions (labeled S1, S2, and S3) in the PTP1B-IRK structure, are shown in ball-and-stick representation. Carbon atoms are colored cyan (PTP1B from PTP1B-IRK), orange (PTP1B from 1G1F), or magenta (phosphopeptide from 1G1F), oxygen atoms are colored red, nitrogen atoms are colored blue, phosphorus atoms are colored black, and sulfur atoms are colored green.
  The above figure is reprinted by permission from Cell Press: Structure (Camb) (2005, 13, 1643-1651) copyright 2005.  
  Figure was selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20381358 S.C.Yip, S.Saha, and J.Chernoff (2010).
PTP1B: a double agent in metabolism and oncogenesis.
  Trends Biochem Sci, 35, 442-449.  
18298791 J.den Hertog, A.Ostman, and F.D.Böhmer (2008).
Protein tyrosine phosphatases: regulatory mechanisms.
  FEBS J, 275, 831-847.  
18819921 V.Sangwan, G.N.Paliouras, J.V.Abella, N.Dubé, A.Monast, M.L.Tremblay, and M.Park (2008).
Regulation of the Met Receptor-tyrosine Kinase by the Protein-tyrosine Phosphatase 1B and T-cell Phosphatase.
  J Biol Chem, 283, 34374-34383.  
18716132 X.Lu, R.Malumbres, B.Shields, X.Jiang, K.A.Sarosiek, Y.Natkunam, T.Tiganis, and I.S.Lossos (2008).
PTP1B is a negative regulator of interleukin 4-induced STAT6 signaling.
  Blood, 112, 4098-4108.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time.