PDBsum entry 2b4s

Hydrolase/transferase

PDB id: 2b4s

Contents

Protein chains

289 a.a.

297 a.a.

Ligands

SO4 ×10

Waters ×377

References listed in PDB file

Key reference

• Title: Crystal structure of a complex between protein tyrosine phosphatase 1b and the insulin receptor tyrosine kinase.
• Authors: S.Li, R.S.Depetris, D.Barford, J.Chernoff, S.R.Hubbard.
• Ref.: Structure (Camb), 2005, 13, 1643-1651. [DOI no: 10.1016/j.str.2005.07.019]
• PubMed id: 16271887

Abstract

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.

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.