Tyr66 acts as a conformational switch in the closed-to-open transition of the SHP-2 N-SH2-domain phosphotyrosine-peptide binding cleft.

ABSTRACT:

Background

The N-terminal SH2 domain (N-SH2) of the non-receptor tyrosine phosphatase SHP-2 is involved both in localization of SHP-2 by recognition of phosphotyrosine (pY) peptides and self-inhibition of SHP-2 phosphatase activity through the formation of a protein-protein interface with the phosphatase domain. Mutations that disrupt this interface break the coupling between pY-peptide binding cleft conformation and self-inhibition, thereby increasing both SHP-2 phosphatase activity and pY-peptide binding affinity, and are associated with the congenital condition Noonan syndrome and various pediatric leukemias. To better characterize the molecular process involved in N-SH2 pY-dependent binding, we have applied explicit-solvent molecular dynamics simulations to study the closed-to-

SUBMITTER: Guvench O 

PROVIDER: S-EPMC1847519 | biostudies-literature | 2007 Mar

REPOSITORIES: biostudies-literature