5E8Y: TGF-BETA RECEPTOR TYPE 2 KINASE DOMAIN (E431A,R433A,E485A,K488A,R493A,R495A) IN COMPLEX WITH STAUROSPORINE

Citation:
Abstract
The cytokine TGF-beta 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-beta signals through two transmembrane serine/threonine kinase receptors: TGFbetaR1 and TGFbetaR2. Multiple structures of the TGFbetaR1 kinase domain are known, but the structure of TGFbetaR2 remains unreported. Wild-type TGFbetaR2 kinase domain was refractory to crystallization, leading to the design of two mutated constructs: firstly, a TGFbetaR1 chimeric protein with seven ATP-site residues mutated to their counterparts in TGFbetaR2, and secondly, a reduction of surface entropy through mutation of six charged residues on the surface of the TGFbetaR2 kinase domain to alanines. These yielded apo and inhibitor-bound crystals that diffracted to high resolution (<2 A). Comparison of these structures with those of TGFbetaR1 reveal shared ligand contacts as well as differences in the ATP-binding sites, suggesting strategies for the design of pan and selective TGFbetaR inhibitors.
PDB ID: 5E8YDownload
MMDB ID: 139138
PDB Deposition Date: 2015/10/14
Updated in MMDB: 2016/05
Experimental Method:
x-ray diffraction
Resolution: 2.05  Å
Source Organism:
Similar Structures:
Biological Unit for 5E8Y: monomeric; determined by author and by software (PISA)
Molecular Components in 5E8Y
Label Count Molecule
Protein (1 molecule)
1
Tgf-beta Receptor Type-2(Gene symbol: TGFBR2)
Molecule annotation
Chemical (1 molecule)
1
1
* Click molecule labels to explore molecular sequence information.

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