2shp
From Proteopedia
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|SITE= | |SITE= | ||
|LIGAND= <scene name='pdbligand=CAT:DODECANE-TRIMETHYLAMINE'>CAT</scene> | |LIGAND= <scene name='pdbligand=CAT:DODECANE-TRIMETHYLAMINE'>CAT</scene> | ||
| - | |ACTIVITY= [http://en.wikipedia.org/wiki/Protein-tyrosine-phosphatase Protein-tyrosine-phosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.48 3.1.3.48] | + | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Protein-tyrosine-phosphatase Protein-tyrosine-phosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.48 3.1.3.48] </span> |
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2shp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2shp OCA], [http://www.ebi.ac.uk/pdbsum/2shp PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2shp RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==Overview== | ||
The structure of the SHP-2 tyrosine phosphatase, determined at 2.0 angstroms resolution, shows how its catalytic activity is regulated by its two SH2 domains. In the absence of a tyrosine-phosphorylated binding partner, the N-terminal SH2 domain binds the phosphatase domain and directly blocks its active site. This interaction alters the structure of the N-SH2 domain, disrupting its phosphopeptide-binding cleft. Conversely, interaction of the N-SH2 domain with phosphopeptide disrupts its phosphatase recognition surface. Thus, the N-SH2 domain is a conformational switch; it either binds and inhibits the phosphatase, or it binds phosphoproteins and activates the enzyme. Recognition of bisphosphorylated ligands by the tandem SH2 domains is an integral element of this switch; the C-terminal SH2 domain contributes binding energy and specificity, but it does not have a direct role in activation. | The structure of the SHP-2 tyrosine phosphatase, determined at 2.0 angstroms resolution, shows how its catalytic activity is regulated by its two SH2 domains. In the absence of a tyrosine-phosphorylated binding partner, the N-terminal SH2 domain binds the phosphatase domain and directly blocks its active site. This interaction alters the structure of the N-SH2 domain, disrupting its phosphopeptide-binding cleft. Conversely, interaction of the N-SH2 domain with phosphopeptide disrupts its phosphatase recognition surface. Thus, the N-SH2 domain is a conformational switch; it either binds and inhibits the phosphatase, or it binds phosphoproteins and activates the enzyme. Recognition of bisphosphorylated ligands by the tandem SH2 domains is an integral element of this switch; the C-terminal SH2 domain contributes binding energy and specificity, but it does not have a direct role in activation. | ||
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| - | ==Disease== | ||
| - | Known diseases associated with this structure: Leopard syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176876 176876]], Leukemia, juvenile myelomonocytic OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176876 176876]], Noonan syndrome 1 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176876 176876]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Pluskey, S.]] | [[Category: Pluskey, S.]] | ||
[[Category: Shoelson, S E.]] | [[Category: Shoelson, S E.]] | ||
| - | [[Category: CAT]] | ||
[[Category: insulin signaling]] | [[Category: insulin signaling]] | ||
[[Category: sh2 protein]] | [[Category: sh2 protein]] | ||
[[Category: tyrosine phosphatase]] | [[Category: tyrosine phosphatase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 05:03:01 2008'' |
Revision as of 02:03, 31 March 2008
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| , resolution 2.00Å | |||||||
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| Ligands: | |||||||
| Activity: | Protein-tyrosine-phosphatase, with EC number 3.1.3.48 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
TYROSINE PHOSPHATASE SHP-2
Overview
The structure of the SHP-2 tyrosine phosphatase, determined at 2.0 angstroms resolution, shows how its catalytic activity is regulated by its two SH2 domains. In the absence of a tyrosine-phosphorylated binding partner, the N-terminal SH2 domain binds the phosphatase domain and directly blocks its active site. This interaction alters the structure of the N-SH2 domain, disrupting its phosphopeptide-binding cleft. Conversely, interaction of the N-SH2 domain with phosphopeptide disrupts its phosphatase recognition surface. Thus, the N-SH2 domain is a conformational switch; it either binds and inhibits the phosphatase, or it binds phosphoproteins and activates the enzyme. Recognition of bisphosphorylated ligands by the tandem SH2 domains is an integral element of this switch; the C-terminal SH2 domain contributes binding energy and specificity, but it does not have a direct role in activation.
About this Structure
2SHP is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Crystal structure of the tyrosine phosphatase SHP-2., Hof P, Pluskey S, Dhe-Paganon S, Eck MJ, Shoelson SE, Cell. 1998 Feb 20;92(4):441-50. PMID:9491886
Page seeded by OCA on Mon Mar 31 05:03:01 2008
