1fvr
From Proteopedia
(New page: 200px<br /> <applet load="1fvr" size="450" color="white" frame="true" align="right" spinBox="true" caption="1fvr, resolution 2.2Å" /> '''TIE2 KINASE DOMAIN''...) |
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| - | [[Image:1fvr.gif|left|200px]]<br /> | + | [[Image:1fvr.gif|left|200px]]<br /><applet load="1fvr" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1fvr" size=" | + | |
caption="1fvr, resolution 2.2Å" /> | caption="1fvr, resolution 2.2Å" /> | ||
'''TIE2 KINASE DOMAIN'''<br /> | '''TIE2 KINASE DOMAIN'''<br /> | ||
==Overview== | ==Overview== | ||
| - | BACKGROUND: Angiogenesis, the formation of new vessels from the existing | + | BACKGROUND: Angiogenesis, the formation of new vessels from the existing vasculature, is a critical process during early development as well as in a number of disease processes. Tie2 (also known as Tek) is an endothelium-specific receptor tyrosine kinase involved in both angiogenesis and vasculature maintenance. RESULTS: We have determined the crystal structure of the Tie2 kinase domain to 2.2 A resolution. The structure contains the catalytic core, the kinase insert domain (KID), and the C-terminal tail. The overall fold is similar to that observed in other serine/threonine and tyrosine kinase structures; however, several unique features distinguish the Tie2 structure from those of other kinases. The Tie2 nucleotide binding loop is in an inhibitory conformation, which is not seen in other kinase structures, while its activation loop adopts an "activated-like" conformation in the absence of phosphorylation. Tyr-897, located in the N-terminal domain, may negatively regulate the activity of Tie2 by preventing dimerization of the kinase domains or by recruiting phosphatases when it is phosphorylated. CONCLUSION: Regulation of the kinase activity of Tie2 is a complex process. Conformational changes in the nucleotide binding loop, activation loop, C helix, and the C-terminal tail are required for ATP and substrate binding. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1FVR is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. 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:// | + | 1FVR is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. 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=1FVR OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Davis, R.]] | [[Category: Davis, R.]] | ||
[[Category: Ellis, B.]] | [[Category: Ellis, B.]] | ||
| - | [[Category: Hassell, A | + | [[Category: Hassell, A M.]] |
| - | [[Category: Holmes, W | + | [[Category: Holmes, W D.]] |
| - | [[Category: Horne, E | + | [[Category: Horne, E L.]] |
| - | [[Category: Kadwell, S | + | [[Category: Kadwell, S H.]] |
| - | [[Category: McKee, D | + | [[Category: McKee, D D.]] |
| - | [[Category: Moore, J | + | [[Category: Moore, J T.]] |
| - | [[Category: Shewchuk, L | + | [[Category: Shewchuk, L M.]] |
[[Category: tyrosine kinase]] | [[Category: tyrosine kinase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:43:10 2008'' |
Revision as of 10:43, 21 February 2008
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TIE2 KINASE DOMAIN
Contents |
Overview
BACKGROUND: Angiogenesis, the formation of new vessels from the existing vasculature, is a critical process during early development as well as in a number of disease processes. Tie2 (also known as Tek) is an endothelium-specific receptor tyrosine kinase involved in both angiogenesis and vasculature maintenance. RESULTS: We have determined the crystal structure of the Tie2 kinase domain to 2.2 A resolution. The structure contains the catalytic core, the kinase insert domain (KID), and the C-terminal tail. The overall fold is similar to that observed in other serine/threonine and tyrosine kinase structures; however, several unique features distinguish the Tie2 structure from those of other kinases. The Tie2 nucleotide binding loop is in an inhibitory conformation, which is not seen in other kinase structures, while its activation loop adopts an "activated-like" conformation in the absence of phosphorylation. Tyr-897, located in the N-terminal domain, may negatively regulate the activity of Tie2 by preventing dimerization of the kinase domains or by recruiting phosphatases when it is phosphorylated. CONCLUSION: Regulation of the kinase activity of Tie2 is a complex process. Conformational changes in the nucleotide binding loop, activation loop, C helix, and the C-terminal tail are required for ATP and substrate binding.
Disease
Known diseases associated with this structure: Venous malformations, multiple cutaneous and mucosal OMIM:[600221]
About this Structure
1FVR is a Single protein structure of sequence from Homo sapiens. 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
Structure of the Tie2 RTK domain: self-inhibition by the nucleotide binding loop, activation loop, and C-terminal tail., Shewchuk LM, Hassell AM, Ellis B, Holmes WD, Davis R, Horne EL, Kadwell SH, McKee DD, Moore JT, Structure. 2000 Nov 15;8(11):1105-13. PMID:11080633
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