Your browser doesn't support javascript.

Portal Regional da BVS

Informação e Conhecimento para a Saúde

Home > Pesquisa > ()
XML
Imprimir Exportar

Formato de exportação:

Exportar

Email
Adicionar mais destinatários
| |

Crystal structures of apo and inhibitor-bound TGFßR2 kinase domain: insights into TGFßR isoform selectivity.

Acta Crystallogr D Struct Biol; 72(Pt 5): 658-74, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-27139629
The cytokine TGF-ß modulates a number of cellular activities and plays a critical role in development, hemostasis and physiology, as well as in diseases including cancer and fibrosis. TGF-ß signals through two transmembrane serine/threonine kinase receptors: TGFßR1 and TGFßR2. Multiple structures of the TGFßR1 kinase domain are known, but the structure of TGFßR2 remains unreported. Wild-type TGFßR2 kinase domain was refractory to crystallization, leading to the design of two mutated constructs: firstly, a TGFßR1 chimeric protein with seven ATP-site residues mutated to their counterparts in TGFßR2, and secondly, a reduction of surface entropy through mutation of six charged residues on the surface of the TGFßR2 kinase domain to alanines. These yielded apo and inhibitor-bound crystals that diffracted to high resolution (<2 Å). Comparison of these structures with those of TGFßR1 reveal shared ligand contacts as well as differences in the ATP-binding sites, suggesting strategies for the design of pan and selective TGFßR inhibitors.