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| {{STRUCTURE_1lkk| PDB=1lkk | SCENE= }} | | {{STRUCTURE_1lkk| PDB=1lkk | SCENE= }} |
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| '''HUMAN P56-LCK TYROSINE KINASE SH2 DOMAIN IN COMPLEX WITH THE PHOSPHOTYROSYL PEPTIDE AC-PTYR-GLU-GLU-ILE (PYEEI PEPTIDE)'''
| | ===HUMAN P56-LCK TYROSINE KINASE SH2 DOMAIN IN COMPLEX WITH THE PHOSPHOTYROSYL PEPTIDE AC-PTYR-GLU-GLU-ILE (PYEEI PEPTIDE)=== |
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| ==Overview==
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| 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.
| | The line below this paragraph, {{ABSTRACT_PUBMED_8604142}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 8604142 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_8604142}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Single protein]] | | [[Category: Single protein]] |
| [[Category: Tong, L.]] | | [[Category: Tong, L.]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 00:00:34 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jul 2 21:19:35 2008'' |