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Details for article 16 of 25 found articles
| Title: |
Molecular Dynamics Simulations on the Free and Complexed N-Terminal SH2 Domain of SHP-2 |
| Author: |
Karin Wieligmann Luis Felipe Pineda De Castro Martin Zacharias |
| Appeared in: |
In silico biology |
| Paging: | Volume 2 (2002) nr. 3 pages 305-311 |
| Year: |
2002-12-28 |
| Contents: |
Signal transduction events are often mediated by small protein domains such as SH2 (Src homology 2) domains that recognize phosphotyrosines (pY) and flanking sequences. In case of the SHP-2 receptor tyrosine phosphatase an N-terminal SH2 domain binds and inactivates the phosphatase (PTP) domain. The pY-peptide- binding site on the N-terminal SH2 domain does not overlap with the PTP binding region. Nevertheless, pY-peptide binding causes domain dissociation and phosphatase activation. Comparative multi-nanosecond molecular dynam-ics simulations on the N-SH2 domain in ligand-bound and free states have been performed to study the allosteric mechanism that leads to domain dissociation upon pY-peptide binding. Significant ligand-dependent differences in the conformational flexibility of regions that are involved in SH2-PTP domain association have been observed. The results support a mechanism of signal transduction where SH2-peptide binding modulates the domain flexibility and reduces its capacity to fit into the entrance of the PTP catalytic domain of SHP-2. |
| Publisher: |
IOS Press |
| Source file: |
Elektronische Wetenschappelijke Tijdschriften |
Details for article 16 of 25 found articles
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