title: Fluorescein Derivatives as Bifunctional Molecules for the Simultaneous Inhibiting and Labeling of FTO Protein.
abstract: The FTO protein is unequivocally reported to play a critical role in human obesity and in the regulation of cellular levels of m(6)A modification, which makes FTO a significant and worthy subject of study. Here, we identified that fluorescein derivatives can selectively inhibit FTO demethylation, and the mechanisms behind these activities were elucidated after we determined the X-ray crystal structures of FTO/fluorescein and FTO/5-aminofluorescein. Furthermore, these inhibitors can also be applied to the direct labeling and enrichment of FTO protein combined with photoaffinity labeling assay.
authors.forename: Tianlu
authors.initials: T
authors.lastname: Wang
authors.forename: Tingting
authors.initials: T
authors.lastname: Hong
authors.affiliation: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , Shanghai 201203, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Huang
authors.forename: Haomiao
authors.initials: H
authors.lastname: Su
authors.forename: Fan
authors.initials: F
authors.lastname: Wu
authors.forename: Yi
authors.initials: Y
authors.lastname: Chen
authors.forename: Lai
authors.initials: L
authors.lastname: Wei
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.forename: Xiaoluan
authors.initials: X
authors.lastname: Hua
authors.forename: Yu
authors.initials: Y
authors.lastname: Xia
authors.forename: Jinglei
authors.initials: J
authors.lastname: Xu
authors.affiliation: School of Life Sciences, Fudan University , Shanghai 200433, China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Gan
authors.forename: Bifeng
authors.initials: B
authors.lastname: Yuan
authors.forename: Yuqi
authors.initials: Y
authors.lastname: Feng
authors.forename: Xiaolian
authors.initials: X
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , Shanghai 201203, China.
authors.forename: Cai-Guang
authors.initials: CG
authors.lastname: Yang
authors.forename: Xiang
authors.initials: X
authors.lastname: Zhou
mesh_terms: D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D018360:Crystallography, X-Ray; D004305:Dose-Response Relationship, Drug; D019793:Fluorescein / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D011506:Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D011506:Proteins; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human; D019793:Fluorescein