1mw4
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(New page: 200px<br /> <applet load="1mw4" size="450" color="white" frame="true" align="right" spinBox="true" caption="1mw4" /> '''Solution structure of the human Grb7-SH2 do...)
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Revision as of 16:09, 12 November 2007
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Solution structure of the human Grb7-SH2 domain in complex with a 10 amino acid peptide pY1139
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Overview
The solution structure of the hGrb7-SH2 domain in complex with a ten amino, acid phosphorylated peptide ligand representative of the erbB2 receptor, tyrosine kinase (pY1139) is presented as determined by nuclear magnetic, resonance methods. The hGrb7-SH2 domain structure reveals the Src homology, 2 domain topology consisting of a central beta-sheet capped at each end by, an alpha-helix. The presence of a four residue insertion in the region, between beta-strand E and the EF loop and resulting influences on the SH2, domain/peptide complex structure are discussed. The binding conformation, of the erbB2 peptide is in a beta-turn similar to that found in, phosphorylated tyrosine peptides bound to the Grb2-SH2 domain. To our, knowledge this is only the second example of an SH2 domain binding its, naturally occurring ligands in a turn, instead of extended, conformation., Close contacts between residues responsible for binding specificity in, hGrb7-SH2 and the erbB2 peptide are characterized and the potential effect, of mutation of these residues on the hGrb7-SH2 domain structure is, discussed.
Disease
Known diseases associated with this structure: Adenocarcinoma of lung, somatic OMIM:[164870], Gastric cancer, somatic OMIM:[164870], Glioblastoma, somatic OMIM:[164870], Ovarian cancer, somatic, OMIM:[164870], Sialidosis, type I OMIM:[608272], Sialidosis, type II OMIM:[608272]
About this Structure
1MW4 is a Protein complex structure of sequences from Homo sapiens. Active as Transferase, with EC number and 2.7.10.2 2.7.10.1 and 2.7.10.2 Full crystallographic information is available from OCA.
Reference
Solution structure of the human Grb7-SH2 domain/erbB2 peptide complex and structural basis for Grb7 binding to ErbB2., Ivancic M, Daly RJ, Lyons BA, J Biomol NMR. 2003 Nov;27(3):205-19. PMID:12975581
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