title: Identification of A Novel Small-Molecule Binding Site of the Fat Mass and Obesity Associated Protein (FTO).
abstract: N-(5-Chloro-2,4-dihydroxyphenyl)-1-phenylcyclobutanecarboxamide (N-CDPCB, 1a) is found to be an inhibitor of the fat mass and obesity associated protein (FTO). The crystal structure of human FTO with 1a reveals a novel binding site for the FTO inhibitor and defines the molecular basis for recognition by FTO of the inhibitor. The identification of the new binding site offers new opportunities for further development of selective and potent inhibitors of FTO, which is expected to provide information concerning novel therapeutic targets for treatment of obesity or obesity-associated diseases.
authors: College of Chemistry and Molecular Engineering, Zhengzhou University , Zhengzhou 450001, PR China.
authors: Wu
authors: W
authors: He
authors: School of Life Sciences, Tsinghua University , Beijing 100084, PR China.|Tsinghua-Peking Center for Life Sciences , Beijing 100084, PR China.
authors: Bin
authors: B
authors: Zhou
authors: School of Life Sciences, Tsinghua University , Beijing 100084, PR China.|Tsinghua-Peking Center for Life Sciences , Beijing 100084, PR China.
authors: Weijia
authors: W
authors: Liu
authors: Space Biology Research and Technology Center, Engineering Research Center of Space Biology, China Academy of Space Technology , Beijing 100190, PR China.
authors: Meizi
authors: M
authors: Zhang
authors: College of Chemistry and Molecular Engineering, Zhengzhou University , Zhengzhou 450001, PR China.
authors: Zhenhua
authors: Z
authors: Shen
authors: School of Life Sciences, Tsinghua University , Beijing 100084, PR China.|Tsinghua-Peking Center for Life Sciences , Beijing 100084, PR China.
authors: Zhifu
authors: Z
authors: Han
authors: College of Chemistry and Molecular Engineering, Zhengzhou University , Zhengzhou 450001, PR China.
authors: Qingwei
authors: Q
authors: Jiang
authors: College of Chemistry and Molecular Engineering, Zhengzhou University , Zhengzhou 450001, PR China.|Collaborative Innovation Center of New Drug Research and Safety Evaluation , Henan Province, Zhengzhou 450001, PR China.
authors: Qinghua
authors: Q
authors: Yang
authors: College of Chemistry and Molecular Engineering, Zhengzhou University , Zhengzhou 450001, PR China.
authors: Chuanjun
authors: C
authors: Song
authors: College of Chemistry and Molecular Engineering, Zhengzhou University , Zhengzhou 450001, PR China.
authors: Ruiyong
authors: R
authors: Wang
authors: School of Life Sciences, Tsinghua University , Beijing 100084, PR China.|Tsinghua-Peking Center for Life Sciences , Beijing 100084, PR China.
authors: Tianhui
authors: T
authors: Niu
authors: Basic Medical College, Zhengzhou University , Zhengzhou 450001, PR China.
authors: Shengna
authors: S
authors: Han
authors: Basic Medical College, Zhengzhou University , Zhengzhou 450001, PR China.
authors: Lirong
authors: L
authors: Zhang
authors: College of Chemistry and Molecular Engineering, Zhengzhou University , Zhengzhou 450001, PR China.
authors: Jie
authors: J
authors: Wu
authors: Space Biology Research and Technology Center, Engineering Research Center of Space Biology, China Academy of Space Technology , Beijing 100190, PR China.
authors: Feima
authors: F
authors: Guo
authors: Space Biology Research and Technology Center, Engineering Research Center of Space Biology, China Academy of Space Technology , Beijing 100190, PR China.
authors: Renbin
authors: R
authors: Zhao
authors: College of Chemistry and Molecular Engineering, Zhengzhou University , Zhengzhou 450001, PR China.
authors: Wenquan
authors: W
authors: Yu
authors: School of Life Sciences, Tsinghua University , Beijing 100084, PR China.|Tsinghua-Peking Center for Life Sciences , Beijing 100084, PR China.
authors: Jijie
authors: J
authors: Chai
authors: College of Chemistry and Molecular Engineering, Zhengzhou University , Zhengzhou 450001, PR China.|Collaborative Innovation Center of New Drug Research and Safety Evaluation , Henan Province, Zhengzhou 450001, PR China.
authors: Junbiao
authors: J
authors: Chang
mesh_terms: D041721:3T3-L1 Cells; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D000627:Aminophenols / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000813:Anilides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites; D018360:Crystallography, X-Ray; D062126:Databases, Chemical; D006801:Humans; D008745:Methylation; D051379:Mice; D008958:Models, Molecular; D011485:Protein Binding; D011506:Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry; D012313:RNA / Q000737:chemistry; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D000627:Aminophenols; D000813:Anilides; C000603797:N-(5-chloro-2,4-dihydroxyphenyl)-1-phenylcyclobutanecarboxamide; D011506:Proteins; D012333:RNA, Messenger; D012313:RNA; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human