View source for 1cwd

[[Image:1cwd.gif|left|200px]]<br /><applet load="1cwd" size="350" color="white" frame="true" align="right" spinBox="true" 
caption="1cwd, resolution 2.25&Aring;" />
'''HUMAN P56LCK TYROSINE KINASE COMPLEXED WITH PHOSPHONOPEPTIDE'''<br />

==Overview==
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.

==Disease==
Known disease associated with this structure: SCID due to LCK deficiency OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=153390 153390]]

==About this Structure==
1CWD is a [http://en.wikipedia.org/wiki/Single_protein 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=1CWD 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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=7532720 7532720]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Mikol, V.]]
[[Category: complex (phosphotransferase/peptide)]]
[[Category: phosphotransferase]]

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:10:25 2008''