2shp
From Proteopedia
(New page: 200px<br /> <applet load="2shp" size="450" color="white" frame="true" align="right" spinBox="true" caption="2shp, resolution 2.00Å" /> '''TYROSINE PHOSPHATAS...) |
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| - | [[Image:2shp.gif|left|200px]]<br /> | + | [[Image:2shp.gif|left|200px]]<br /><applet load="2shp" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="2shp" size=" | + | |
caption="2shp, resolution 2.00Å" /> | caption="2shp, resolution 2.00Å" /> | ||
'''TYROSINE PHOSPHATASE SHP-2'''<br /> | '''TYROSINE PHOSPHATASE SHP-2'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The structure of the SHP-2 tyrosine phosphatase, determined at 2.0 | + | 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. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2SHP 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 CAT as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [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] Full crystallographic information is available from [http:// | + | 2SHP 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=CAT:'>CAT</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2SHP OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Dhe-Paganon, S.]] | [[Category: Dhe-Paganon, S.]] | ||
| - | [[Category: Eck, M | + | [[Category: Eck, M J.]] |
[[Category: Hof, P.]] | [[Category: Hof, P.]] | ||
[[Category: Pluskey, S.]] | [[Category: Pluskey, S.]] | ||
| - | [[Category: Shoelson, S | + | [[Category: Shoelson, S E.]] |
[[Category: CAT]] | [[Category: CAT]] | ||
[[Category: insulin signaling]] | [[Category: insulin signaling]] | ||
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[[Category: tyrosine phosphatase]] | [[Category: tyrosine phosphatase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:49:11 2008'' |
Revision as of 16:49, 21 February 2008
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TYROSINE PHOSPHATASE SHP-2
Contents |
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.
Disease
Known diseases associated with this structure: Leopard syndrome OMIM:[176876], Leukemia, juvenile myelomonocytic OMIM:[176876], Noonan syndrome 1 OMIM:[176876]
About this Structure
2SHP is a Single protein structure of sequence from Homo sapiens with as ligand. Active as Protein-tyrosine-phosphatase, with EC number 3.1.3.48 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
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