1he7

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|SITE=
|SITE=
|LIGAND= <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>
|LIGAND= <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>
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|ACTIVITY= [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]
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|ACTIVITY= <span class='plainlinks'>[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] </span>
|GENE=
|GENE=
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|DOMAIN=
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|RELATEDENTRY=
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1he7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1he7 OCA], [http://www.ebi.ac.uk/pdbsum/1he7 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1he7 RCSB]</span>
}}
}}
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==Overview==
==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.
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.
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==Disease==
 
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Known diseases associated with this structure: Insensitivity to pain, congenital, with anhidrosis OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=191315 191315]], Medullary thyroid carcinoma, familial OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=191315 191315]]
 
==About this Structure==
==About this Structure==
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[[Category: Tyler, S J.]]
[[Category: Tyler, S J.]]
[[Category: Wilcock, G K.]]
[[Category: Wilcock, G K.]]
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[[Category: GOL]]
 
[[Category: nerve growth factor]]
[[Category: nerve growth factor]]
[[Category: strand-swapping]]
[[Category: strand-swapping]]
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[[Category: trk-receptor]]
[[Category: trk-receptor]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 11:35:57 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 21:03:16 2008''

Revision as of 18:03, 30 March 2008


PDB ID 1he7

Drag the structure with the mouse to rotate
, resolution 2.0Å
Ligands:
Activity: Transferase, with EC number and 2.7.10.2 2.7.10.1 and 2.7.10.2
Resources: FirstGlance, OCA, PDBsum, RCSB
Coordinates: save as pdb, mmCIF, xml



HUMAN NERVE GROWTH FACTOR RECEPTOR TRKA


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.

About this Structure

1HE7 is a Single protein structure of sequence from Homo sapiens. 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

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