Nuclear Techniques ›› 2016, Vol. 39 ›› Issue (8): 80101-080101.doi: 10.11889/j.0253-3219.2016.hjs.39.080101

• SYNCHROTRON RADIATION TECHNOLOGY AND APPLICATIONS •     Next Articles

Crystallography study of the complexes of human fatty acid binding protein 4 with aspirin and its derivative

HUANG Pei1,2, LI Minjun1, ZUO Gang1, GUO Haojie1,2, ZHOU Huan1, XIE Muyun1, YU Feng1, XU Chunyan1, HE Jianhua1   

  1. 1 Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Zhangjiang Campus, Shanghai 201204, China;
    2 University of Chinese Academy of Sciences, Beijing 100049, China
  • Received:2016-04-18 Revised:2016-04-28 Online:2016-08-10 Published:2016-08-15
  • About author:HUANG Pei, female, born in 1990, graduated from Northwestern University in 2013, master student, focusing on macromolecular crystallography
  • Supported by:

    Supported by National Natural Science Foundation of China (No.31100528, No.31371260)

Abstract:

Background: Fatty acid binding protein 4 (FABP4), as fatty acid chaperone, plays center roles in lipid transport, lipolysis and liposynthesis, and it has been proved to be involved in the lipid signaling and inflammatory responses. Inhibitors of FABP4 are promising treatments for the diabetes and atherosclerosis. Purpose: The aim is to reveal the structural conformation of aspirin and salicylic acid binding to the FABP4, and to explore the novel structural features for the design of high-selective FABP4 inhibitors. Methods: Single crystal X-ray diffraction is applied to solve the structure of the ligand-protein complexes. Results: We have determined the crystal structures of FABP4 in complex with aspirin and its derivative, and from which a special C-H-π interaction between the residues Phe16, Arg126 and the benzyl ring of aspirin has been defined. Conclusion: The complex structures of FABP4 bound with aspirin and its derivative show that the edge-to-face C-H-π interaction between the residues Phe16, Arg126 and the benzyl ring of aspirin is a critical intermolecular force between the ligand-FABP4 interactions, which enables us to consciously apply these interactions in hit and lead optimization in rational structure based drug design.

Key words: FABP4, Protein crystallography, C-H-&pi, interaction

CLC Number: 

  • TL99