3bu5: Difference between revisions
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|PDB= 3bu5 |SIZE=350|CAPTION= <scene name='initialview01'>3bu5</scene>, resolution 2.10Å | |PDB= 3bu5 |SIZE=350|CAPTION= <scene name='initialview01'>3bu5</scene>, resolution 2.10Å | ||
|SITE= <scene name='pdbsite=AC1:Mg+Binding+Site+For+Residue+A+301'>AC1</scene> and <scene name='pdbsite=AC2:Atp+Binding+Site+For+Residue+A+300'>AC2</scene> | |SITE= <scene name='pdbsite=AC1:Mg+Binding+Site+For+Residue+A+301'>AC1</scene> and <scene name='pdbsite=AC2:Atp+Binding+Site+For+Residue+A+300'>AC2</scene> | ||
|LIGAND= <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene> | |LIGAND= <scene name='pdbligand=ATP:ADENOSINE-5'-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene> | ||
|ACTIVITY= [http://en.wikipedia.org/wiki/Receptor_protein-tyrosine_kinase Receptor protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 2.7.10.1] | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Receptor_protein-tyrosine_kinase Receptor protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 2.7.10.1] </span> | ||
|GENE= INSR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= INSR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
|DOMAIN= | |||
|RELATEDENTRY=[[3bu3|3BU3]], [[3bu6|3BU6]] | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3bu5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bu5 OCA], [http://www.ebi.ac.uk/pdbsum/3bu5 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=3bu5 RCSB]</span> | |||
}} | }} | ||
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==Overview== | ==Overview== | ||
Insulin receptor substrates 1 and 2 (IRS1 and -2) are crucial adaptor proteins in mediating the metabolic and mitogenic effects of insulin and insulin-like growth factor 1. These proteins consist of a pleckstrin homology domain, a phosphotyrosine binding domain and a C-terminal region containing numerous sites of tyrosine, serine and threonine phosphorylation. Previous yeast two-hybrid studies identified a region unique to IRS2, termed the kinase regulatory-loop binding (KRLB) region, which interacts with the tyrosine kinase domain of the insulin receptor. Here we present the crystal structure of the insulin receptor kinase in complex with a 15-residue peptide from the KRLB region. In the structure, this segment of IRS2 is bound in the kinase active site with Tyr628 positioned for phosphorylation. Although Tyr628 was phosphorylated by the insulin receptor, its catalytic turnover was poor, resulting in kinase inhibition. Our studies indicate that the KRLB region functions to limit tyrosine phosphorylation of IRS2. | Insulin receptor substrates 1 and 2 (IRS1 and -2) are crucial adaptor proteins in mediating the metabolic and mitogenic effects of insulin and insulin-like growth factor 1. These proteins consist of a pleckstrin homology domain, a phosphotyrosine binding domain and a C-terminal region containing numerous sites of tyrosine, serine and threonine phosphorylation. Previous yeast two-hybrid studies identified a region unique to IRS2, termed the kinase regulatory-loop binding (KRLB) region, which interacts with the tyrosine kinase domain of the insulin receptor. Here we present the crystal structure of the insulin receptor kinase in complex with a 15-residue peptide from the KRLB region. In the structure, this segment of IRS2 is bound in the kinase active site with Tyr628 positioned for phosphorylation. Although Tyr628 was phosphorylated by the insulin receptor, its catalytic turnover was poor, resulting in kinase inhibition. Our studies indicate that the KRLB region functions to limit tyrosine phosphorylation of IRS2. | ||
==Disease== | |||
Known disease associated with this structure: Diabetes mellitus, insulin-resistant, with acanthosis nigricans OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=147670 147670]], Hyperinsulinemic hypoglycemia, familial, 5 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=147670 147670]], Leprechaunism OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=147670 147670]], Rabson-Mendenhall syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=147670 147670]] | |||
==About this Structure== | ==About this Structure== | ||
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[[Category: Hubbard, S R.]] | [[Category: Hubbard, S R.]] | ||
[[Category: Wu, J.]] | [[Category: Wu, J.]] | ||
[[Category: alternative splicing]] | [[Category: alternative splicing]] | ||
[[Category: atp]] | [[Category: atp]] | ||
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[[Category: tyrosine-protein kinase]] | [[Category: tyrosine-protein kinase]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 05:29:03 2008'' | ||
Revision as of 05:29, 31 March 2008
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| , resolution 2.10Å | |||||||
|---|---|---|---|---|---|---|---|
| Sites: | and | ||||||
| Ligands: | , , | ||||||
| Gene: | INSR (Homo sapiens) | ||||||
| Activity: | Receptor protein-tyrosine kinase, with EC number 2.7.10.1 | ||||||
| Related: | 3BU3, 3BU6
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of the insulin receptor kinase in complex with IRS2 KRLB peptide and ATP
OverviewOverview
Insulin receptor substrates 1 and 2 (IRS1 and -2) are crucial adaptor proteins in mediating the metabolic and mitogenic effects of insulin and insulin-like growth factor 1. These proteins consist of a pleckstrin homology domain, a phosphotyrosine binding domain and a C-terminal region containing numerous sites of tyrosine, serine and threonine phosphorylation. Previous yeast two-hybrid studies identified a region unique to IRS2, termed the kinase regulatory-loop binding (KRLB) region, which interacts with the tyrosine kinase domain of the insulin receptor. Here we present the crystal structure of the insulin receptor kinase in complex with a 15-residue peptide from the KRLB region. In the structure, this segment of IRS2 is bound in the kinase active site with Tyr628 positioned for phosphorylation. Although Tyr628 was phosphorylated by the insulin receptor, its catalytic turnover was poor, resulting in kinase inhibition. Our studies indicate that the KRLB region functions to limit tyrosine phosphorylation of IRS2.
DiseaseDisease
Known disease associated with this structure: Diabetes mellitus, insulin-resistant, with acanthosis nigricans OMIM:[147670], Hyperinsulinemic hypoglycemia, familial, 5 OMIM:[147670], Leprechaunism OMIM:[147670], Rabson-Mendenhall syndrome OMIM:[147670]
About this StructureAbout this Structure
3BU5 is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Structural and biochemical characterization of the KRLB region in insulin receptor substrate-2., Wu J, Tseng YD, Xu CF, Neubert TA, White MF, Hubbard SR, Nat Struct Mol Biol. 2008 Mar;15(3):251-8. Epub 2008 Feb 17. PMID:18278056
Page seeded by OCA on Mon Mar 31 05:29:03 2008
Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)
OCA- Pages with broken file links
- Homo sapiens
- Protein complex
- Receptor protein-tyrosine kinase
- Hubbard, S R.
- Wu, J.
- Alternative splicing
- Atp
- Atp-binding
- Carbohydrate metabolism
- Cleavage on pair of basic residue
- Diabetes mellitus
- Disease mutation
- Glycoprotein
- Insulin receptor
- Irk
- Irs2
- Kinase
- Krlb
- Membrane
- Nucleotide-binding
- Peptide
- Phosphoprotein
- Polymorphism
- Substrate
- Transducer
- Transferase
- Transmembrane
- Tyrosine-protein kinase