title: Echinomycin, a potential binder of FKBP12, shows minor effect on calcineurin activity.
abstract: Echinomycin, a member of the quinoxaline family of antibiotics, is known to be a small-molecule inhibitor of hypoxia inducible factor-1 (HIF-1) DNA binding activity. Recently, it has been shown to suppress mammalian target of rapamycin (mTOR) signaling and growth in leukemia cell lines. In this study, we investigated whether echinomycin interacts with the FKBP12 protein. Molecular docking was used, and the predicted binding energy was -10.61 kcal/mol. Moreover, surface plasmon resonance imaging and fluorescence quenching techniques were used to validate this interaction. Echinomycin binds to FKBP12 with a strong binding affinity comparable with rapamycin. Furthermore, the echinomycin-FKBP12 complex has been shown to affect calcineurin activity when tested in a calcineurin phosphatase inhibition assay. All of these studies have shown that echinomycin may have a double impact on HIF signaling by direct inhibition and through mTOR.
authors.affiliation: National Center for Nanoscience and Technology, Beijing, People's Republic of China University of Chinese Academy of Sciences, Beijing, People's Republic of China.
authors.forename: Vikramjeet
authors.initials: V
authors.lastname: Singh
authors.affiliation: National Center for Nanoscience and Technology, Beijing, People's Republic of China University of Chinese Academy of Sciences, Beijing, People's Republic of China.
authors.forename: Amita
authors.initials: A
authors.lastname: Nand
authors.affiliation: Chinese Academy of Sciences Key Laboratory of Pathogenic Microbiology & Immunology, Institute of Microbiology, CAS, Beijing, People's Republic of China.
authors.forename: Caixia
authors.initials: C
authors.lastname: Chen
authors.affiliation: College of Life Science and Bioengineering, Beijing University of Technology, Beijing, People's Republic of China.
authors.forename: ZhiPeng
authors.initials: Z
authors.lastname: Li
authors.affiliation: Key Laboratory of Bioinformatics, School of Life Sciences, Tsinghua University, Beijing, People's Republic of China.
authors.forename: Sheng-Jie
authors.initials: SJ
authors.lastname: Li
authors.affiliation: National Center for Nanoscience and Technology, Beijing, People's Republic of China School of Chemistry and Chemical Engineering, Shanxi University, Taiyuan, People's Republic of China.
authors.forename: Songbai
authors.initials: S
authors.lastname: Wang
authors.affiliation: National Center for Nanoscience and Technology, Beijing, People's Republic of China University of Chinese Academy of Sciences, Beijing, People's Republic of China.
authors.forename: Mo
authors.initials: M
authors.lastname: Yang
authors.affiliation: National Center for Nanoscience and Technology, Beijing, People's Republic of China University of Chinese Academy of Sciences, Beijing, People's Republic of China.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Merino
authors.affiliation: Chinese Academy of Sciences Key Laboratory of Pathogenic Microbiology & Immunology, Institute of Microbiology, CAS, Beijing, People's Republic of China.
authors.forename: Lixin
authors.initials: L
authors.lastname: Zhang
authors.affiliation: National Center for Nanoscience and Technology, Beijing, People's Republic of China University of Chinese Academy of Sciences, Beijing, People's Republic of China jizhu@nanoctr.cn.
authors.forename: Jingsong
authors.initials: J
authors.lastname: Zhu
mesh_terms: D019703:Calcineurin / Q000737:chemistry / Q000378:metabolism*; D004448:Echinomycin / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D008954:Models, Biological; D008958:Models, Molecular; D008968:Molecular Conformation; D062105:Molecular Docking Simulation; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D011485:Protein Binding; D015203:Reproducibility of Results; D015398:Signal Transduction / Q000187:drug effects; D020349:Surface Plasmon Resonance / Q000379:methods; D022061:Tacrolimus Binding Protein 1A / Q000378:metabolism*
chemical_list: D004448:Echinomycin; C120817:calcineurin phosphatase; D019703:Calcineurin; D010744:Phosphoric Monoester Hydrolases; D022061:Tacrolimus Binding Protein 1A
keywords: FK506-FKBP12-calcineurin; SPRi; echinomycin; fluorescence quenching; mTOR