1agw
From Proteopedia
(New page: 200px<br /> <applet load="1agw" size="450" color="white" frame="true" align="right" spinBox="true" caption="1agw, resolution 2.4Å" /> '''CRYSTAL STRUCTURE OF...) |
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| - | [[Image:1agw.gif|left|200px]]<br /> | + | [[Image:1agw.gif|left|200px]]<br /><applet load="1agw" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1agw" size=" | + | |
caption="1agw, resolution 2.4Å" /> | caption="1agw, resolution 2.4Å" /> | ||
'''CRYSTAL STRUCTURE OF THE TYROSINE KINASE DOMAIN OF FIBROBLAST GROWTH FACTOR RECEPTOR 1 IN COMPLEX WITH SU4984 INHIBITOR'''<br /> | '''CRYSTAL STRUCTURE OF THE TYROSINE KINASE DOMAIN OF FIBROBLAST GROWTH FACTOR RECEPTOR 1 IN COMPLEX WITH SU4984 INHIBITOR'''<br /> | ||
==Overview== | ==Overview== | ||
| - | A new class of protein tyrosine kinase inhibitors was identified that is | + | A new class of protein tyrosine kinase inhibitors was identified that is based on an oxindole core (indolinones). Two compounds from this class inhibited the kinase activity of fibroblast growth factor receptor 1 (FGFR1) and showed differential specificity toward other receptor tyrosine kinases. Crystal structures of the tyrosine kinase domain of FGFR1 in complex with the two compounds were determined. The oxindole occupies the site in which the adenine of adenosine triphosphate binds, whereas the moieties that extend from the oxindole contact residues in the hinge region between the two kinase lobes. The more specific inhibitor of FGFR1 induces a conformational change in the nucleotide-binding loop. This structural information will facilitate the design of new inhibitors for use in the treatment of cancer and other diseases in which cell signaling by tyrosine kinases plays a crucial role in disease pathogenesis. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1AGW is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with SU2 as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [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] Full crystallographic information is available from [http:// | + | 1AGW is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=SU2:'>SU2</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1AGW OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Transferase]] | [[Category: Transferase]] | ||
| - | [[Category: Hubbard, S | + | [[Category: Hubbard, S R.]] |
[[Category: Mohammadi, M.]] | [[Category: Mohammadi, M.]] | ||
[[Category: Schlessinger, J.]] | [[Category: Schlessinger, J.]] | ||
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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 11:44:21 2008'' |
Revision as of 09:44, 21 February 2008
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CRYSTAL STRUCTURE OF THE TYROSINE KINASE DOMAIN OF FIBROBLAST GROWTH FACTOR RECEPTOR 1 IN COMPLEX WITH SU4984 INHIBITOR
Contents |
Overview
A new class of protein tyrosine kinase inhibitors was identified that is based on an oxindole core (indolinones). Two compounds from this class inhibited the kinase activity of fibroblast growth factor receptor 1 (FGFR1) and showed differential specificity toward other receptor tyrosine kinases. Crystal structures of the tyrosine kinase domain of FGFR1 in complex with the two compounds were determined. The oxindole occupies the site in which the adenine of adenosine triphosphate binds, whereas the moieties that extend from the oxindole contact residues in the hinge region between the two kinase lobes. The more specific inhibitor of FGFR1 induces a conformational change in the nucleotide-binding loop. This structural information will facilitate the design of new inhibitors for use in the treatment of cancer and other diseases in which cell signaling by tyrosine kinases plays a crucial role in disease pathogenesis.
Disease
Known diseases associated with this structure: Atopic dermatitis, susceptibility to OMIM:[135940], Ichthyosis vulgaris OMIM:[135940], Jackson-Weiss syndrome OMIM:[136350], Kallmann syndrome 2 OMIM:[136350], Pfeiffer syndrome OMIM:[136350]
About this Structure
1AGW is a Single protein structure of sequence from Homo sapiens with as ligand. Active as Transferase, with EC number and 2.7.10.2 2.7.10.1 and 2.7.10.2 Full crystallographic information is available from OCA.
Reference
Structures of the tyrosine kinase domain of fibroblast growth factor receptor in complex with inhibitors., Mohammadi M, McMahon G, Sun L, Tang C, Hirth P, Yeh BK, Hubbard SR, Schlessinger J, Science. 1997 May 9;276(5314):955-60. PMID:9139660
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