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Molecular mechanism of interaction between fatty acid delta 6 desaturase and acyl-CoA by computational prediction

  • Jie Cui (Creator)
  • Haiqin Chen (Creator)
  • Xin Tang (Creator)
  • Hao Zhang (Creator)
  • Yong Q. Chen (Creator)
  • Wei Chen (North West Agriculture and Forestry University, 'Ministry of Education of the People's Republic of China', Tongji Hospital of Tongji University Branch, Jiangnan University, Second Affiliated Hospital of Soochow University, Wayne State University, Zhejiang University, Liaoning Cancer Hospital & Institute, Chengdu University of Traditional Chinese Medicine, Huazhong Agricultural University, The First Affiliated Hospital of Sun Yat-sen University, Department of Physics, The University of Texas at Arlington, Sun Yat-Sen University, Ministry of Agriculture, Zimbabwe, Roche (Switzerland), Shanghai Tenth People's Hospital, Affiliated Hospital of Nantong University, East China University of Science and Technology, Fudan University, Physiologie de la Reproduction et des Comportements, Central South University, Chinese Center for Disease Control and Prevention, Ningbo University, Guangzhou Women and Children Medical Center, Institute of Dermatology and Hospital for Skin Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Qingdao Agricultural University, Chinese Academy of Sciences, Jilin University, Chia-Yi Christian Hospital, Hebei United University, Nanjing University, Fudan University Shanghai Cancer Center, Beijing Technology and Business University, Shanghai Jiao Tong University) (Creator)

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Abstract Enzyme catalyzed desaturation of intracellular fatty acids plays an important role in various physiological and pathological processes related to lipids. Limited to the multiple transmembrane domains, it is difficult to obtain their three-dimensional structure of fatty acid desaturases. So how they interact with their substrates is unclear. Here, we predicted the complex of Micromonas pusilla delta 6 desaturase (MpFADS6) with the substrate linoleinyl-CoA (ALA-CoA) by trRosetta software and docking poses by Dock 6 software. The potential enzyme–substrate binding sites were anchored by analysis of the complex. Then, site-directed mutagenesis and activity verification clarified that W290, W224, and F352 were critical residues of the substrate tunnel and directly bonded to ALA-CoA. H94 and H69 were indispensable for transporting electrons with heme. H452, N445, and H358 significantly influenced the recognition and attraction of MpFADS6 to the substrate. These findings provide new insights and methods to determine the structure, mechanisms and directed transformation of membrane-bound desaturases. Graphical Abstract
Date made available2022
Publisherfigshare

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