1lkl
From Proteopedia
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| - | [[Image:1lkl.jpg|left|200px]] | + | [[Image:1lkl.jpg|left|200px]] |
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| - | '''HUMAN P56-LCK TYROSINE KINASE SH2 DOMAIN IN COMPLEX WITH THE PHOSPHOTYROSYL PEPTIDE AC-PTYR-GLU-GLU-GLY (PYEEG PEPTIDE)''' | + | {{Structure |
| + | |PDB= 1lkl |SIZE=350|CAPTION= <scene name='initialview01'>1lkl</scene>, resolution 1.8Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene> and <scene name='pdbligand=PHS:PHOSPHONIC ACID'>PHS</scene> | ||
| + | |ACTIVITY= | ||
| + | |GENE= | ||
| + | }} | ||
| + | |||
| + | '''HUMAN P56-LCK TYROSINE KINASE SH2 DOMAIN IN COMPLEX WITH THE PHOSPHOTYROSYL PEPTIDE AC-PTYR-GLU-GLU-GLY (PYEEG PEPTIDE)''' | ||
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==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1LKL is a [ | + | 1LKL is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LKL OCA]. |
==Reference== | ==Reference== | ||
| - | Crystal structures of the human p56lck SH2 domain in complex with two short phosphotyrosyl peptides at 1.0 A and 1.8 A resolution., Tong L, Warren TC, King J, Betageri R, Rose J, Jakes S, J Mol Biol. 1996 Mar 1;256(3):601-10. PMID:[http:// | + | Crystal structures of the human p56lck SH2 domain in complex with two short phosphotyrosyl peptides at 1.0 A and 1.8 A resolution., Tong L, Warren TC, King J, Betageri R, Rose J, Jakes S, J Mol Biol. 1996 Mar 1;256(3):601-10. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/8604142 8604142] |
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: complex (tyrosine kinase/peptide)]] | [[Category: complex (tyrosine kinase/peptide)]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 12:31:57 2008'' |
Revision as of 10:31, 20 March 2008
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| , resolution 1.8Å | |||||||
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| Ligands: | and | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
HUMAN P56-LCK TYROSINE KINASE SH2 DOMAIN IN COMPLEX WITH THE PHOSPHOTYROSYL PEPTIDE AC-PTYR-GLU-GLU-GLY (PYEEG PEPTIDE)
Contents |
Overview
src homology 2 (SH2) domains are modules of about 100 amino acid residues and bind to phosphotyrosine-containing motifs in a sequence-specific manner. They play important roles in intracellular signal transduction and represent potential targets for pharmacological intervention. The protein tyrosine kinase p56lck is a member of the src family and is involved in T-cell activation. The crystal structure of its SH2 domain with an 11-residue peptide showed that the phosphotyrosine and the Ile residue at the pY + 3 position are recognized by the SH2 domain. We present here the crystal structure of the SH2 domain of human p56lck in complex with the short phosphotyrosyl peptide Ac-pTyr-Glu-Glu-Ile (pYEEI peptide) at 1.0 A resolution. The structural analysis at atomic resolution reveals that residue Arg134 (alphaA2), which interacts with the phosphotyrosine side-chain, is present in two conformations in the complex. The structure at 1.8 A resolution of the complex with the phosphotyrosyl peptide Ac-pTyr-Glu-Glu-Gly (pYEEG peptide), which is 11 fold less potent, shows another binding mode for the pY + 3 residue as well as rearrangements of the side-chain of Arg196 (EF3) and one of the water molecules at the base of the pY + 3 pocket. The structure of the complex with the short pYEEI peptide at atomic resolution represents a good starting point for the design and optimization of new inhibitors. Comparative structural analysis of many different inhibitor complexes will be an important component of this drug discovery process.
Disease
Known disease associated with this structure: SCID due to LCK deficiency OMIM:[153390]
About this Structure
1LKL is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Crystal structures of the human p56lck SH2 domain in complex with two short phosphotyrosyl peptides at 1.0 A and 1.8 A resolution., Tong L, Warren TC, King J, Betageri R, Rose J, Jakes S, J Mol Biol. 1996 Mar 1;256(3):601-10. PMID:8604142
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