| Full text | |
| Author(s): |
Sanches, Karoline
;
Dias, Raphael V. R.
;
da Silva, Paulo H.
;
Caruso, Icaro P.
;
Fossey, Marcelo A.
;
de Souza, Fatima P.
;
de Oliveira, Leandro C.
;
Melo, Fernando A.
Total Authors: 8
|
| Document type: | Journal article |
| Source: | Journal of Molecular Structure; v. 1234, p. 10-pg., 2021-03-06. |
| Abstract | |
The adaptor protein growth factor-bound protein 2 (Grb2) is an important regulator of the fibroblast growth factor receptor 2 (FGFR2) before extracellular stimuli. It is known to form complexes that end up in the mitogen-activated protein kinase (MAPK) pathway activation, which is involved in proliferation and oncogenic signal transduction. Grb2 is a versatile protein performing functions other than adaptor protein, making it a relevant target to verify its interaction with flavonoids such as Rutin and Morin. These small polyphenols molecules are easy to be found in the nature and its anti-tumor properties are well-known. By using fluorescence spectroscopy, the thermodynamic profile of the interaction between those molecules and Grb2 showed entropically driven interactions, where hydrophobic effects take place as the main interaction potential. The dissociation constants found were K-d similar to 10(-6) M for Morin and K-d similar to 10(-5) M for Rutin. The molar ratio protein/ligand is 1:1 for both assays. Furthermore, nuclear magnetic resonance has provided important information about the protein-ligand interaction epitopes, which has been used as a guide for molecular docking and molecular dynamics simulations. The combination of the obtained results shows the SH2 domain as the most probable interaction place on Grb2 dimer for Rutin and Morin binding. Sh2 is a well-known domain responsible for pY (phosphotyrosine) recognition upon protein partners and an important protein module for testing SH2 domain inhibitors. (C) 2021 Elsevier B.V. All rights reserved. (AU) | |
| FAPESP's process: | 16/08753-6 - Evaluating kinase mechanisms and related proteins |
| Grantee: | Raphael Vinicius Rodrigues Dias |
| Support Opportunities: | Scholarships in Brazil - Master |
| FAPESP's process: | 14/17630-0 - Functional studies of tyrosine kinase fibroblast growth factor receptor (FGFR2), the adapter growth factor receptor-Bound protein 2 (Grb2) and tyrosine phosphatase SHP2 |
| Grantee: | Fernando Alves de Melo |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 19/24974-0 - Function studies of Grb2 through nuclear magnetic resonance and fluorescence: correlating dynamics and structure |
| Grantee: | Fernando Alves de Melo |
| Support Opportunities: | Regular Research Grants |