2np8
From Proteopedia
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|PDB= 2np8 |SIZE=350|CAPTION= <scene name='initialview01'>2np8</scene>, resolution 2.25Å | |PDB= 2np8 |SIZE=350|CAPTION= <scene name='initialview01'>2np8</scene>, resolution 2.25Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= | + | |LIGAND= <scene name='pdbligand=CC3:N-{3-[(4-{[3-(TRIFLUOROMETHYL)PHENYL]AMINO}PYRIMIDIN-2-YL)AMINO]PHENYL}CYCLOPROPANECARBOXAMIDE'>CC3</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene> |
| - | |ACTIVITY= [http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] | + | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span> |
|GENE= AIK ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= AIK ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1mq4|1MQ4]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2np8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2np8 OCA], [http://www.ebi.ac.uk/pdbsum/2np8 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2np8 RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==Overview== | ||
The 2.25 A crystal structure of a complex of Aurora A kinase (AIKA) with cyclopropanecarboxylic acid-(3-(4-(3-trifluoromethyl-phenylamino)-pyrimidin-2-ylamino)-phenyl)-am ide 1 is described here. The inhibitor binding mode is novel, with the cyclopropanecarboxylic acid moiety directed towards the solvent exposed region of the ATP-binding pocket, and several induced structural changes in the active-site compared with other published AIK structures. This structure provides context for the available SAR data on this compound class, and could be exploited for the design of analogs with increased affinity and selectivity for AIK. | The 2.25 A crystal structure of a complex of Aurora A kinase (AIKA) with cyclopropanecarboxylic acid-(3-(4-(3-trifluoromethyl-phenylamino)-pyrimidin-2-ylamino)-phenyl)-am ide 1 is described here. The inhibitor binding mode is novel, with the cyclopropanecarboxylic acid moiety directed towards the solvent exposed region of the ATP-binding pocket, and several induced structural changes in the active-site compared with other published AIK structures. This structure provides context for the available SAR data on this compound class, and could be exploited for the design of analogs with increased affinity and selectivity for AIK. | ||
| - | |||
| - | ==Disease== | ||
| - | Known diseases associated with this structure: Colon cancer, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=603072 603072]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Swanson, R V.]] | [[Category: Swanson, R V.]] | ||
[[Category: Tari, L W.]] | [[Category: Tari, L W.]] | ||
| - | [[Category: CC3]] | ||
| - | [[Category: SO4]] | ||
[[Category: aik]] | [[Category: aik]] | ||
[[Category: aurora 2 kinase]] | [[Category: aurora 2 kinase]] | ||
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[[Category: kinase inhibitor]] | [[Category: kinase inhibitor]] | ||
| - | ''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 04:06:19 2008'' |
Revision as of 01:06, 31 March 2008
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| , resolution 2.25Å | |||||||
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| Ligands: | , | ||||||
| Gene: | AIK (Homo sapiens) | ||||||
| Activity: | Non-specific serine/threonine protein kinase, with EC number 2.7.11.1 | ||||||
| Related: | 1MQ4
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Structural Basis for the Inhibition of Aurora A Kinase by a Novel Class of High Affinity Disubstituted Pyrimidine Inhibitors
Overview
The 2.25 A crystal structure of a complex of Aurora A kinase (AIKA) with cyclopropanecarboxylic acid-(3-(4-(3-trifluoromethyl-phenylamino)-pyrimidin-2-ylamino)-phenyl)-am ide 1 is described here. The inhibitor binding mode is novel, with the cyclopropanecarboxylic acid moiety directed towards the solvent exposed region of the ATP-binding pocket, and several induced structural changes in the active-site compared with other published AIK structures. This structure provides context for the available SAR data on this compound class, and could be exploited for the design of analogs with increased affinity and selectivity for AIK.
About this Structure
2NP8 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structural basis for the inhibition of Aurora A kinase by a novel class of high affinity disubstituted pyrimidine inhibitors., Tari LW, Hoffman ID, Bensen DC, Hunter MJ, Nix J, Nelson KJ, McRee DE, Swanson RV, Bioorg Med Chem Lett. 2007 Feb 1;17(3):688-91. Epub 2006 Nov 2. PMID:17157005
Page seeded by OCA on Mon Mar 31 04:06:19 2008
