1nzv
From Proteopedia
(New page: 200px<br /><applet load="1nzv" size="450" color="white" frame="true" align="right" spinBox="true" caption="1nzv, resolution 2.10Å" /> '''Crystal Structure of...) |
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| - | [[Image:1nzv.jpg|left|200px]]<br /><applet load="1nzv" size=" | + | [[Image:1nzv.jpg|left|200px]]<br /><applet load="1nzv" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1nzv, resolution 2.10Å" /> | caption="1nzv, resolution 2.10Å" /> | ||
'''Crystal Structure of Src SH2 domain bound to doubly phosphorylated peptide PQpYIpYVPA'''<br /> | '''Crystal Structure of Src SH2 domain bound to doubly phosphorylated peptide PQpYIpYVPA'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Recruitment of the Src kinase to the activated form of the | + | Recruitment of the Src kinase to the activated form of the platelet-derived growth factor (PDGF) receptor involves recognition of a unique sequence motif in the juxtamembrane region of the receptor by the Src homology 2 (SH2) domain of the enzyme. This motif contains two phosphotyrosine residues separated by one residue (sequence pYIpYV where pY indicates a phosphotyrosine). Here, we provide the thermodynamic and structural basis for the binding of this motif by the Src SH2 domain. We show that the second phosphorylation event increases the free energy window for specific interaction and that the physiological target is exquisitely designed for the task of recruiting specifically an SH2 domain which otherwise demonstrates very little intrinsic ability to discriminate sequences C-terminal to the first phosphorylation event. Surprisingly, we show that water plays a role in the recognition process. |
==About this Structure== | ==About this Structure== | ||
| - | 1NZV is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Rous_sarcoma_virus Rous sarcoma virus] with CL and PG4 as [http://en.wikipedia.org/wiki/ligands ligands]. 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:// | + | 1NZV is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Rous_sarcoma_virus Rous sarcoma virus] with <scene name='pdbligand=CL:'>CL</scene> and <scene name='pdbligand=PG4:'>PG4</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. 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=1NZV OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Transferase]] | [[Category: Transferase]] | ||
| - | [[Category: Lubman, O | + | [[Category: Lubman, O Y.]] |
[[Category: Waksman, G.]] | [[Category: Waksman, G.]] | ||
[[Category: CL]] | [[Category: CL]] | ||
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[[Category: sh2 domain]] | [[Category: sh2 domain]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:11:50 2008'' |
Revision as of 12:11, 21 February 2008
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Crystal Structure of Src SH2 domain bound to doubly phosphorylated peptide PQpYIpYVPA
Overview
Recruitment of the Src kinase to the activated form of the platelet-derived growth factor (PDGF) receptor involves recognition of a unique sequence motif in the juxtamembrane region of the receptor by the Src homology 2 (SH2) domain of the enzyme. This motif contains two phosphotyrosine residues separated by one residue (sequence pYIpYV where pY indicates a phosphotyrosine). Here, we provide the thermodynamic and structural basis for the binding of this motif by the Src SH2 domain. We show that the second phosphorylation event increases the free energy window for specific interaction and that the physiological target is exquisitely designed for the task of recruiting specifically an SH2 domain which otherwise demonstrates very little intrinsic ability to discriminate sequences C-terminal to the first phosphorylation event. Surprisingly, we show that water plays a role in the recognition process.
About this Structure
1NZV is a Single protein structure of sequence from Rous sarcoma virus with and as ligands. 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
Structural and thermodynamic basis for the interaction of the Src SH2 domain with the activated form of the PDGF beta-receptor., Lubman OY, Waksman G, J Mol Biol. 2003 May 2;328(3):655-68. PMID:12706723
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