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New page: left|200px<br /><applet load="2pnb" size="450" color="white" frame="true" align="right" spinBox="true" caption="2pnb" /> '''STRUCTURE OF AN SH2 DOMAIN OF THE P85 ALPHA ...
 
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[[Image:2pnb.gif|left|200px]]<br /><applet load="2pnb" size="450" color="white" frame="true" align="right" spinBox="true"  
[[Image:2pnb.gif|left|200px]]<br /><applet load="2pnb" size="350" color="white" frame="true" align="right" spinBox="true"  
caption="2pnb" />
caption="2pnb" />
'''STRUCTURE OF AN SH2 DOMAIN OF THE P85 ALPHA SUBUNIT OF PHOSPHATIDYLINOSITOL-3-OH KINASE'''<br />
'''STRUCTURE OF AN SH2 DOMAIN OF THE P85 ALPHA SUBUNIT OF PHOSPHATIDYLINOSITOL-3-OH KINASE'''<br />


==Overview==
==Overview==
Receptor protein-tyrosine kinases, through phosphorylation of specific, tyrosine residues, generate high-affinity binding sites which direct, assembly of multienzyme signalling complexes. Many of these signalling, proteins, including phospholipase C gamma, GTPase-activating protein and, phosphatidylinositol-3-OH kinase, contain src-homology 2 (SH2) domains, which bind with high affinity and specificity to tyrosine-phosphorylated, sequences. The critical role played by SH2 domains in signalling has been, highlighted by recent studies showing that mutation of specific, phosphorylation sites on the platelet-derived growth factor receptor, impair its association with phosphatidylinositol-3-OH kinase, preventing, growth factor-induced mitogenesis. Here we report the solution structure, of an isolated SH2 domain from the 85K regulatory subunit of, phosphatidylinositol-3-OH kinase, determined using multidimensional, nuclear magnetic resonance spectroscopy. The structure is characterized by, a central region of beta-sheet flanked by two alpha-helices, with a highly, flexible loop close to functionally important residues previously, identified by site-directed mutagenesis.
Receptor protein-tyrosine kinases, through phosphorylation of specific tyrosine residues, generate high-affinity binding sites which direct assembly of multienzyme signalling complexes. Many of these signalling proteins, including phospholipase C gamma, GTPase-activating protein and phosphatidylinositol-3-OH kinase, contain src-homology 2 (SH2) domains, which bind with high affinity and specificity to tyrosine-phosphorylated sequences. The critical role played by SH2 domains in signalling has been highlighted by recent studies showing that mutation of specific phosphorylation sites on the platelet-derived growth factor receptor impair its association with phosphatidylinositol-3-OH kinase, preventing growth factor-induced mitogenesis. Here we report the solution structure of an isolated SH2 domain from the 85K regulatory subunit of phosphatidylinositol-3-OH kinase, determined using multidimensional nuclear magnetic resonance spectroscopy. The structure is characterized by a central region of beta-sheet flanked by two alpha-helices, with a highly flexible loop close to functionally important residues previously identified by site-directed mutagenesis.


==About this Structure==
==About this Structure==
2PNB is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Active as [http://en.wikipedia.org/wiki/Phosphatidylinositol_3-kinase Phosphatidylinositol 3-kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.137 2.7.1.137] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2PNB OCA].  
2PNB is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Active as [http://en.wikipedia.org/wiki/Phosphatidylinositol_3-kinase Phosphatidylinositol 3-kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.137 2.7.1.137] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2PNB OCA].  


==Reference==
==Reference==
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[[Category: Phosphatidylinositol 3-kinase]]
[[Category: Phosphatidylinositol 3-kinase]]
[[Category: Single protein]]
[[Category: Single protein]]
[[Category: Booker, G.W.]]
[[Category: Booker, G W.]]
[[Category: Breeze, A.L.]]
[[Category: Breeze, A L.]]
[[Category: Campbell, I.D.]]
[[Category: Campbell, I D.]]
[[Category: Downing, A.K.]]
[[Category: Downing, A K.]]
[[Category: Gout, I.]]
[[Category: Gout, I.]]
[[Category: Panayotou, G.]]
[[Category: Panayotou, G.]]
[[Category: Waterfield, M.D.]]
[[Category: Waterfield, M D.]]
[[Category: signalling protein]]
[[Category: signalling protein]]


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