1he7
From Proteopedia
(New page: 200px<br /> <applet load="1he7" size="450" color="white" frame="true" align="right" spinBox="true" caption="1he7, resolution 2.0Å" /> '''HUMAN NERVE GROWTH F...) |
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| - | [[Image:1he7.gif|left|200px]]<br /> | + | [[Image:1he7.gif|left|200px]]<br /><applet load="1he7" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1he7" size=" | + | |
caption="1he7, resolution 2.0Å" /> | caption="1he7, resolution 2.0Å" /> | ||
'''HUMAN NERVE GROWTH FACTOR RECEPTOR TRKA'''<br /> | '''HUMAN NERVE GROWTH FACTOR RECEPTOR TRKA'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Nerve growth factor (NGF) is involved in the development and maintenance | + | Nerve growth factor (NGF) is involved in the development and maintenance of the nervous system and has been implicated as a possible therapeutic target molecule in a number of neurodegenerative diseases, especially Alzheimer's disease. NGF binds with high affinity to the extracellular region of a tyrosine kinase receptor, TrkA, which comprises three leucine-rich motifs (LRMs), flanked by two cysteine-rich clusters, followed by two immunoglobulin-like (Ig-like) domains. We have expressed the second Ig-like domain as a recombinant protein in E. coli and demonstrate that NGF binds to this domain with similar affinity to the native receptor. This domain (TrkAIg(2)) has the ability to sequester NGF in vitro, preventing NGF-induced neurite outgrowth, and in vivo, inhibiting NGF-induced plasma extravasation. We also present the three-dimensional structure of the TrkAIg(2) domain in a new crystal form, refined to 2.0 A resolution. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1HE7 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 GOL 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:// | + | 1HE7 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=GOL:'>GOL</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=1HE7 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Transferase]] | [[Category: Transferase]] | ||
| - | [[Category: Allen, S | + | [[Category: Allen, S J.]] |
| - | [[Category: Banfield, M | + | [[Category: Banfield, M J.]] |
| - | [[Category: Bennett, G | + | [[Category: Bennett, G S.]] |
| - | [[Category: Brady, R | + | [[Category: Brady, R L.]] |
| - | [[Category: Brain, S | + | [[Category: Brain, S D.]] |
| - | [[Category: Clarke, A | + | [[Category: Clarke, A R.]] |
| - | [[Category: Dando, J | + | [[Category: Dando, J A.]] |
| - | [[Category: Holden, P | + | [[Category: Holden, P H.]] |
[[Category: Mason, G.]] | [[Category: Mason, G.]] | ||
| - | [[Category: Naylor, R | + | [[Category: Naylor, R L.]] |
[[Category: Robertson, A.]] | [[Category: Robertson, A.]] | ||
| - | [[Category: Tyler, S | + | [[Category: Tyler, S J.]] |
| - | [[Category: Wilcock, G | + | [[Category: Wilcock, G K.]] |
[[Category: GOL]] | [[Category: GOL]] | ||
[[Category: nerve growth factor]] | [[Category: nerve growth factor]] | ||
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[[Category: trk-receptor]] | [[Category: trk-receptor]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:00:20 2008'' |
Revision as of 11:00, 21 February 2008
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HUMAN NERVE GROWTH FACTOR RECEPTOR TRKA
Contents |
Overview
Nerve growth factor (NGF) is involved in the development and maintenance of the nervous system and has been implicated as a possible therapeutic target molecule in a number of neurodegenerative diseases, especially Alzheimer's disease. NGF binds with high affinity to the extracellular region of a tyrosine kinase receptor, TrkA, which comprises three leucine-rich motifs (LRMs), flanked by two cysteine-rich clusters, followed by two immunoglobulin-like (Ig-like) domains. We have expressed the second Ig-like domain as a recombinant protein in E. coli and demonstrate that NGF binds to this domain with similar affinity to the native receptor. This domain (TrkAIg(2)) has the ability to sequester NGF in vitro, preventing NGF-induced neurite outgrowth, and in vivo, inhibiting NGF-induced plasma extravasation. We also present the three-dimensional structure of the TrkAIg(2) domain in a new crystal form, refined to 2.0 A resolution.
Disease
Known diseases associated with this structure: Insensitivity to pain, congenital, with anhidrosis OMIM:[191315], Medullary thyroid carcinoma, familial OMIM:[191315]
About this Structure
1HE7 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
Identification and structure of the nerve growth factor binding site on TrkA., Robertson AG, Banfield MJ, Allen SJ, Dando JA, Mason GG, Tyler SJ, Bennett GS, Brain SD, Clarke AR, Naylor RL, Wilcock GK, Brady RL, Dawbarn D, Biochem Biophys Res Commun. 2001 Mar 23;282(1):131-41. PMID:11263982
Page seeded by OCA on Thu Feb 21 13:00:20 2008
Categories: Homo sapiens | Single protein | Transferase | Allen, S J. | Banfield, M J. | Bennett, G S. | Brady, R L. | Brain, S D. | Clarke, A R. | Dando, J A. | Holden, P H. | Mason, G. | Naylor, R L. | Robertson, A. | Tyler, S J. | Wilcock, G K. | GOL | Nerve growth factor | Strand-swapping | Trk-receptor
