Structure-based discovery of neoandrographolide as a novel inhibitor of Rab5 to suppress cancer growth
Jing Zhang, Yue Sun, Liye Zhong, Nan‐Nan Yu, Lan Ouyang, Run‐Dong Fang, Yang Wang, Qing‐Yu He
Abstract
mutation of Ser34 decreased the stabilization of Rab5. Moreover, fluorescence titration experiment and isothermal titration calorimetry (ITC) assay revealed a direct binding between NAP and Rab5. Biochemical and cell-based assays showed that NAP treatment not only diminished the activity of Rab5, but also suppressed cell growth of cancer cell. This finding firstly identifies NAP as a novel inhibitor of Rab5, which directly binds with Rab5 by occupying the GDP/GTP binding groove to suppress its functions, highlighting a great potential of NAP to be developed as a chemotherapeutic agent in cancer therapy.
Topics & Concepts
ChemistryIn silicoIsothermal titration calorimetryGTP'GTPaseNapCancer researchSmall GTPaseSignal transductionBiochemistryBiologyEnzymeGeneNeuroscienceCellular transport and secretionBiochemical and Structural CharacterizationSignaling Pathways in Disease