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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Conformational change of organic cofactor PLP is essential for catalysis in PLP-dependent enzymes

  • Ngo, Ho-Phuong-Thuy (Department of Biological Sciences, Konkuk University) ;
  • Nguyen, Diem Quynh (Department of Biological Sciences, Konkuk University) ;
  • Park, Hyunjae (Department of Biological Sciences, Konkuk University) ;
  • Park, Yoon Sik (Department of Biological Sciences, Konkuk University) ;
  • Kwak, Kiwoong (Department of Biological Sciences, Konkuk University) ;
  • Kim, Taejoon (Department of Biological Sciences, Konkuk University) ;
  • Lee, Jang Ho (Department of Biological Sciences, Konkuk University) ;
  • Cho, Kyoung Sang (Department of Biological Sciences, Konkuk University) ;
  • Kang, Lin-Woo (Department of Biological Sciences, Konkuk University)
  • Received : 2022.05.25
  • Accepted : 2022.07.11
  • Published : 2022.09.30
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Abstract

Pyridoxal 5'-phosphate (PLP)-dependent enzymes are ubiquitous, catalyzing various biochemical reactions of approximately 4% of all classified enzymatic activities. They transform amines and amino acids into important metabolites or signaling molecules and are important drug targets in many diseases. In the crystal structures of PLP-dependent enzymes, organic cofactor PLP showed diverse conformations depending on the catalytic step. The conformational change of PLP is essential in the catalytic mechanism. In the study, we review the sophisticated catalytic mechanism of PLP, especially in transaldimination reactions. Most drugs targeting PLP-dependent enzymes make a covalent bond to PLP with the transaldimination reaction. A detailed understanding of organic cofactor PLP will help develop a new drug against PLP-dependent enzymes.

Keywords

Acknowledgement

This work was supported by the Bio & Medical Technology Development Program of the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT (NRF-2017M3A9E4078017) and by the project 'Development of biomedical materials based on marine proteins' (Project No. 20170305), funded by the Ministry of Oceans and Fisheries, Korea (J.-H.L.). This work was also supported by the Konkuk University Research Fund (A0190023) in 2020 [2020-A019-0268 (K.S.C., T.K., J.H.L. and D.Q.N.)].

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