1gag: Difference between revisions
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[[Image:1gag.gif|left|200px]] | [[Image:1gag.gif|left|200px]] | ||
'''CRYSTAL STRUCTURE OF THE INSULIN RECEPTOR KINASE IN COMPLEX WITH A BISUBSTRATE INHIBITOR''' | {{Structure | ||
|PDB= 1gag |SIZE=350|CAPTION= <scene name='initialview01'>1gag</scene>, resolution 2.7Å | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene> and <scene name='pdbligand=112:THIOPHOSPHORIC ACID O-((ADENOSYL-PHOSPHO)PHOSPHO)-S-ACETAMIDYL-DIESTER'>112</scene> | |||
|ACTIVITY= [http://en.wikipedia.org/wiki/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 and 2.7.10.2 2.7.10.1 and 2.7.10.2] | |||
|GENE= | |||
}} | |||
'''CRYSTAL STRUCTURE OF THE INSULIN RECEPTOR KINASE IN COMPLEX WITH A BISUBSTRATE INHIBITOR''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
1GAG is a [ | 1GAG is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1GAG OCA]. | ||
==Reference== | ==Reference== | ||
Mechanism-based design of a protein kinase inhibitor., Parang K, Till JH, Ablooglu AJ, Kohanski RA, Hubbard SR, Cole PA, Nat Struct Biol. 2001 Jan;8(1):37-41. PMID:[http:// | Mechanism-based design of a protein kinase inhibitor., Parang K, Till JH, Ablooglu AJ, Kohanski RA, Hubbard SR, Cole PA, Nat Struct Biol. 2001 Jan;8(1):37-41. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/11135668 11135668] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: tyrosine kinase]] | [[Category: tyrosine kinase]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 11:20:28 2008'' | ||
Revision as of 09:20, 20 March 2008
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| 1gag, resolution 2.7Å | |||||||||||||
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| Ligands: | MG and 112 | ||||||||||||
| Activity: | Transferase, with EC number and 2.7.10.2 2.7.10.1 and 2.7.10.2 | ||||||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||||||
CRYSTAL STRUCTURE OF THE INSULIN RECEPTOR KINASE IN COMPLEX WITH A BISUBSTRATE INHIBITOR
Overview
Protein kinase inhibitors have applications as anticancer therapeutic agents and biological tools in cell signaling. Based on a phosphoryl transfer mechanism involving a dissociative transition state, a potent and selective bisubstrate inhibitor for the insulin receptor tyrosine kinase was synthesized by linking ATPgammaS to a peptide substrate analog via a two-carbon spacer. The compound was a high affinity competitive inhibitor against both nucleotide and peptide substrates and showed a slow off-rate. A crystal structure of this inhibitor bound to the tyrosine kinase domain of the insulin receptor confirmed the key design features inspired by a dissociative transition state, and revealed that the linker takes part in the octahedral coordination of an active site Mg2+. These studies suggest a general strategy for the development of selective protein kinase inhibitors.
Disease
Known diseases 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 Structure
1GAG is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Mechanism-based design of a protein kinase inhibitor., Parang K, Till JH, Ablooglu AJ, Kohanski RA, Hubbard SR, Cole PA, Nat Struct Biol. 2001 Jan;8(1):37-41. PMID:11135668
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