Journal:Acta Cryst F:S2053230X24010094

spinqualitylabelsall models Crystal structure of TβRI–SB505124 complex showing the ICD Kinase domain (blue) and SB505124, as spheres with CPK colors, occupying the ATP binding cleft between the kinase N- and C-lobes. Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Human TGFβR1 in complex with kinase inhibitor SB505124 Jhon A. Rodriguez Buitrago, Marene Landstrom, Magnus Wolf-Watz Molecular Tour This study presents the high-resolution crystal structure of the intracellular domain of TGFBR1 in complex with the competitive inhibitor SB505124. The findings provide detailed insights into this complex's molecular interactions and structural configuration, elucidating the mechanisms by which SB505124 inhibits TGFβR1 activity. These insights are significant for understanding the regulation of TGF-β signaling, a pathway critically involved in cancer biology. The manuscript highlights several key points: 1. Structural Insights: We reveal the atomic-level interactions between TGFBR1 and SB505124, offering a comprehensive view of how this inhibitor binds to and affects the receptor's conformation. A comparison of the ICD–SB505124 and ICD–SB431542 complexes is seen in a close-up view. 2. Regulatory Mechanisms: The structural analysis sheds light on the functional implications of SB505124 binding, particularly its role in disrupting TGF-β signaling pathways, which are often deregulated in various cancers. 3. Therapeutic Potential: Based on the structural findings, the potential of SB505124 as a therapeutic agent in cancer treatment is discussed, providing a foundation for future drug development efforts targeting TGFβR1. References

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