2b4s
From Proteopedia
(New page: 200px<br /> <applet load="2b4s" size="450" color="white" frame="true" align="right" spinBox="true" caption="2b4s, resolution 2.30Å" /> '''Crystal structure o...) |
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| - | [[Image:2b4s.gif|left|200px]]<br /> | + | [[Image:2b4s.gif|left|200px]]<br /><applet load="2b4s" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="2b4s" size=" | + | |
caption="2b4s, resolution 2.30Å" /> | caption="2b4s, resolution 2.30Å" /> | ||
'''Crystal structure of a complex between PTP1B and the insulin receptor tyrosine kinase'''<br /> | '''Crystal structure of a complex between PTP1B and the insulin receptor tyrosine kinase'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Protein tyrosine phosphatase 1B (PTP1B) is a highly specific negative | + | 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== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2B4S is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with SO4 as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Protein-tyrosine-phosphatase Protein-tyrosine-phosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.48 3.1.3.48] Full crystallographic information is available from [http:// | + | 2B4S is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=SO4:'>SO4</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Protein-tyrosine-phosphatase Protein-tyrosine-phosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.48 3.1.3.48] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2B4S OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Barford, D.]] | [[Category: Barford, D.]] | ||
[[Category: Chernoff, J.]] | [[Category: Chernoff, J.]] | ||
| - | [[Category: Depetris, R | + | [[Category: Depetris, R S.]] |
| - | [[Category: Hubbard, S | + | [[Category: Hubbard, S R.]] |
[[Category: Li, S.]] | [[Category: Li, S.]] | ||
[[Category: SO4]] | [[Category: SO4]] | ||
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[[Category: tyrosine protein kinase]] | [[Category: tyrosine protein kinase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:34:09 2008'' |
Revision as of 14:34, 21 February 2008
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Crystal structure of a complex between PTP1B and the insulin receptor tyrosine kinase
Contents |
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 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
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