1cwe

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{{STRUCTURE_1cwe| PDB=1cwe | SCENE= }}
{{STRUCTURE_1cwe| PDB=1cwe | SCENE= }}
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'''HUMAN P56LCK TYROSINE KINASE COMPLEXED WITH PHOSPHONOPEPTIDE'''
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===HUMAN P56LCK TYROSINE KINASE COMPLEXED WITH PHOSPHONOPEPTIDE===
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==Overview==
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Src homology-2 (SH2) domains are protein modules found within a wide variety of cytoplasmic signalling molecules that bind with high affinity to phosphotyrosyl-containing protein sequences. In order to develop SH2 inhibitors that contain phosphotyrosyl analogues resistant to cellular phosphatases, we have solved the crystal structures of the SH2 domain of p56lck in separate complexes with two high-affinity p-(phosphonomethyl)phenylalanine-containing peptides. The structures have been determined at 2.3 A and 2.25 A, and refined to crystallographic R-factors of 19.2% and 18.5%, respectively. The conformation of the SH2 domain of p56lck is essentially similar to that observed in Src and Lck complexed with a phosphotyrosine-containing peptide except in some loops and especially in the loop that connects the second and third beta-strands. This loop, which was involved in hydrogen-bond interactions with the phosphotyrosine moiety, has moved away in the phosphonopeptide complexes as a rigid body by about 7 A on two hinges leaving the tyrosine phosphate mimetic moiety accessible to the solvent. Some intramolecular hydrogen bonds with other residues of the third and fourth beta-strands stabilize an open conformation of the lid, suggesting a flap mechanism for peptide binding.
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(as it appears on PubMed at http://www.pubmed.gov), where 7532720 is the PubMed ID number.
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{{ABSTRACT_PUBMED_7532720}}
==About this Structure==
==About this Structure==
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[[Category: Mikol, V.]]
[[Category: Mikol, V.]]
[[Category: Phosphotransferase]]
[[Category: Phosphotransferase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 13:11:08 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jun 30 21:37:16 2008''

Revision as of 18:37, 30 June 2008

Image:1cwe.png

Template:STRUCTURE 1cwe

HUMAN P56LCK TYROSINE KINASE COMPLEXED WITH PHOSPHONOPEPTIDE

Template:ABSTRACT PUBMED 7532720

About this Structure

1CWE is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

The crystal structures of the SH2 domain of p56lck complexed with two phosphonopeptides suggest a gated peptide binding site., Mikol V, Baumann G, Keller TH, Manning U, Zurini MG, J Mol Biol. 1995 Feb 17;246(2):344-55. PMID:7532720

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