Raf1激酶抑制蛋白 RKIP是MAPK和GPCR细胞信号通路的重要调控蛋白。近年来研究表明RKIP与许多肿瘤相关，研究RKIP的抑制剂和激动剂，有助于设计和研发以RKIP为靶点的抗肿瘤新药。我们的前期工作表明：RKIP通过改变配体结合口袋的构象，改变RKIP与Raf1， Grk2 激酶的相互作用，从而调控MAPK和GPCR信号通路。本项目以RKIP的配体结合口袋为活性中心，从药物库里筛选出并用生物薄膜干涉技术验证了四种与RKIP具有高亲和力的配体（Suramin, Cefotetan, Clofazimine, Pranlukast）,进一步用核磁共振技术研究 RKIP与这四种配体的复合物结构和动力学，以及这些配体对RKIP与Raf1, Grk2相互作用的干扰，揭示这些配体调控MAPK和 GPCR信号通路的结构基础和分子机制，为设计和研发用于治疗与RKIP相关疾病的药物提供理论依据。

Raf1 kinase inhibitor protein RKIP is an important regulator in MAPK and GPCR signal pathways. Recent studies show that RKIP is closely related with many diseases. Therefore, exploring inhibitors and agonists of RKIP will help to design and develop new anti-tumour drugs against the RKIP target. Our previous studies demonstrate that, RKIP can adaopt feasible conformation to bind either Raf1 or Grk2 kinase, and regulate MAPK and GPCR signal pathways. Based on the structural characteristics of the ligand-binding pocket of RKIP , we screened out four ligands (Suramin, Cefotetan, Clofazimine, Pranlukast) from the drug library, and determined their binding affinites for RKIP with bio-layer interference technology. Furthermore, we will determine the solution structures and dynamics of the complexes of RKIP with these ligands, and address the intervention role of these ligands on the interactions of RKIP with Raf1 and Grk2 kinases, and then elucidate the structural basis for these ligands regulating MAPK and GPCR signaling pathways. Our results will be helpful for designing and developing novel drugs for treating RKIP related diseases.