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| | {{STRUCTURE_2fgi| PDB=2fgi | SCENE= }} | | {{STRUCTURE_2fgi| PDB=2fgi | SCENE= }} |
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| - | '''CRYSTAL STRUCTURE OF THE TYROSINE KINASE DOMAIN OF FGF RECEPTOR 1 IN COMPLEX WITH INHIBITOR PD173074'''
| + | ===CRYSTAL STRUCTURE OF THE TYROSINE KINASE DOMAIN OF FGF RECEPTOR 1 IN COMPLEX WITH INHIBITOR PD173074=== |
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| - | ==Overview==
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| - | Angiogenesis, the sprouting of new blood vessels from pre-existing ones, is an essential physiological process in development, yet also plays a major role in the progression of human diseases such as diabetic retinopathy, atherosclerosis and cancer. The effects of the most potent angiogenic factors, vascular endothelial growth factor (VEGF), angiopoietin and fibroblast growth factor (FGF) are mediated through cell surface receptors that possess intrinsic protein tyrosine kinase activity. In this report, we describe a synthetic compound of the pyrido[2,3-d]pyrimidine class, designated PD 173074, that selectively inhibits the tyrosine kinase activities of the FGF and VEGF receptors. We show that systemic administration of PD 173074 in mice can effectively block angiogenesis induced by either FGF or VEGF with no apparent toxicity. To elucidate the determinants of selectivity, we have determined the crystal structure of PD 173074 in complex with the tyrosine kinase domain of FGF receptor 1 at 2.5 A resolution. A high degree of surface complementarity between PD 173074 and the hydrophobic, ATP-binding pocket of FGF receptor 1 underlies the potency and selectivity of this inhibitor. PD 173074 is thus a promising candidate for a therapeutic angiogenesis inhibitor to be used in the treatment of cancer and other diseases whose progression is dependent upon new blood vessel formation.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_9774334}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 9774334 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_9774334}} |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: Protein kinase]] | | [[Category: Protein kinase]] |
| | [[Category: Tyrosine-protein kinase]] | | [[Category: Tyrosine-protein kinase]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 03:51:54 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 01:01:14 2008'' |
Revision as of 22:01, 28 July 2008
Template:STRUCTURE 2fgi
CRYSTAL STRUCTURE OF THE TYROSINE KINASE DOMAIN OF FGF RECEPTOR 1 IN COMPLEX WITH INHIBITOR PD173074
Template:ABSTRACT PUBMED 9774334
About this Structure
2FGI is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Crystal structure of an angiogenesis inhibitor bound to the FGF receptor tyrosine kinase domain., Mohammadi M, Froum S, Hamby JM, Schroeder MC, Panek RL, Lu GH, Eliseenkova AV, Green D, Schlessinger J, Hubbard SR, EMBO J. 1998 Oct 15;17(20):5896-904. PMID:9774334
Page seeded by OCA on Tue Jul 29 01:01:14 2008
Categories: Homo sapiens | Single protein | Transferase | Eliseenkova, A V. | Froum, S. | Green, D. | Hamby, J M. | Hubbard, S R. | Lu, G H. | Mohammadi, M. | Panek, R L. | Schlessinger, J. | Schroeder, M. | Atp-binding | Inhibitor | Phosphorylation | Protein kinase | Tyrosine-protein kinase
