2b4s
From Proteopedia
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Crystal structure of a complex between PTP1B and the insulin receptor tyrosine kinase
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Overview
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.
Disease
Known diseases associated with this structure: Abdominal body fat distribution, modifier of OMIM:[176885], Diabetes mellitus, insulin-resistant, with acanthosis nigricans OMIM:[147670], Hyperinsulinemic hypoglycemia, familial, 5 OMIM:[147670], Insulin resistance, susceptibility to OMIM:[176885], Leprechaunism OMIM:[147670], Rabson-Mendenhall syndrome OMIM:[147670]
About this Structure
2B4S is a Protein complex structure of sequences from Homo sapiens with SO4 as ligand. Active as Protein-tyrosine-phosphatase, with EC number 3.1.3.48 Full crystallographic information is available from OCA.
Reference
Crystal structure of a complex between protein tyrosine phosphatase 1B and the insulin receptor tyrosine kinase., Li S, Depetris RS, Barford D, Chernoff J, Hubbard SR, Structure. 2005 Nov;13(11):1643-51. PMID:16271887
Page seeded by OCA on Mon Nov 12 20:58:35 2007
