2oi3
From Proteopedia
(New page: 200px<br /> <applet load="2oi3" size="450" color="white" frame="true" align="right" spinBox="true" caption="2oi3" /> '''NMR Structure Analysis of the Hematopoetic ...) |
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| - | [[Image:2oi3.gif|left|200px]]<br /> | + | [[Image:2oi3.gif|left|200px]]<br /><applet load="2oi3" size="350" color="white" frame="true" align="right" spinBox="true" |
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'''NMR Structure Analysis of the Hematopoetic Cell Kinase SH3 Domain complexed with an artificial high affinity ligand (PD1)'''<br /> | '''NMR Structure Analysis of the Hematopoetic Cell Kinase SH3 Domain complexed with an artificial high affinity ligand (PD1)'''<br /> | ||
==Overview== | ==Overview== | ||
| - | We studied the interaction of hematopoietic cell kinase SH3 domain | + | We studied the interaction of hematopoietic cell kinase SH3 domain (HckSH3) with an artificial 12-residue proline-rich peptide PD1 (HSKYPLPPLPSL) identified as high affinity ligand (K(D)=0.2 muM). PD1 shows an unusual ligand sequence for SH3 binding in type I orientation because it lacks the typical basic anchor residue at position P(-3), but instead has a tyrosine residue at this position. A basic lysine residue, however, is present at position P(-4). The solution structure of the HckSH3:PD1 complex, which is the first HckSH3 complex structure available, clearly reveals that the P(-3) tyrosine residue of PD1 does not take the position of the typical anchor residue but rather forms additional van der Waals interactions with the HckSH3 RT loop. Instead, lysine at position P(-4) of PD1 substitutes the function of the P(-3) anchor residue. This finding expands the well known ligand consensus sequence +xxPpxP by +xxxPpxP. Thus, software tools like iSPOT fail to identify PD1 as a high-affinity HckSH3 ligand so far. In addition, a short antiparallel beta-sheet in the RT loop of HckSH3 is observed upon PD1 binding. The structure of the HckSH3:PD1 complex reveals novel features of SH3 ligand binding and yields new insights into the structural basics of SH3-ligand interactions. Consequences for computational prediction tools adressing SH3-ligand interactions as well as the biological relevance of our findings are discussed. |
==About this Structure== | ==About this Structure== | ||
| - | 2OI3 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 ACE and NH2 as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Non-specific_protein-tyrosine_kinase Non-specific protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.2 2.7.10.2] Full crystallographic information is available from [http:// | + | 2OI3 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=ACE:'>ACE</scene> and <scene name='pdbligand=NH2:'>NH2</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Non-specific_protein-tyrosine_kinase Non-specific protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.2 2.7.10.2] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2OI3 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: src-type tyrosine kinase]] | [[Category: src-type tyrosine kinase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:18:45 2008'' |
Revision as of 16:18, 21 February 2008
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NMR Structure Analysis of the Hematopoetic Cell Kinase SH3 Domain complexed with an artificial high affinity ligand (PD1)
Overview
We studied the interaction of hematopoietic cell kinase SH3 domain (HckSH3) with an artificial 12-residue proline-rich peptide PD1 (HSKYPLPPLPSL) identified as high affinity ligand (K(D)=0.2 muM). PD1 shows an unusual ligand sequence for SH3 binding in type I orientation because it lacks the typical basic anchor residue at position P(-3), but instead has a tyrosine residue at this position. A basic lysine residue, however, is present at position P(-4). The solution structure of the HckSH3:PD1 complex, which is the first HckSH3 complex structure available, clearly reveals that the P(-3) tyrosine residue of PD1 does not take the position of the typical anchor residue but rather forms additional van der Waals interactions with the HckSH3 RT loop. Instead, lysine at position P(-4) of PD1 substitutes the function of the P(-3) anchor residue. This finding expands the well known ligand consensus sequence +xxPpxP by +xxxPpxP. Thus, software tools like iSPOT fail to identify PD1 as a high-affinity HckSH3 ligand so far. In addition, a short antiparallel beta-sheet in the RT loop of HckSH3 is observed upon PD1 binding. The structure of the HckSH3:PD1 complex reveals novel features of SH3 ligand binding and yields new insights into the structural basics of SH3-ligand interactions. Consequences for computational prediction tools adressing SH3-ligand interactions as well as the biological relevance of our findings are discussed.
About this Structure
2OI3 is a Single protein structure of sequence from Homo sapiens with and as ligands. Active as Non-specific protein-tyrosine kinase, with EC number 2.7.10.2 Full crystallographic information is available from OCA.
Reference
Solution structure of a Hck SH3 domain ligand complex reveals novel interaction modes., Schmidt H, Hoffmann S, Tran T, Stoldt M, Stangler T, Wiesehan K, Willbold D, J Mol Biol. 2007 Feb 2;365(5):1517-32. Epub 2006 Nov 10. PMID:17141806
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