Conformational change of organic cofactor PLP is essential for catalysis in PLP-dependent enzymes

• Published in: BMB reports Vol. 55; no. 9; pp. 439 - 446
• Main Authors: Ngo, Ho-Phuong-Thuy, Nguyen, Diem Quynh, Park, Hyunjae, Park, Yoon Sik, Kwak, Kiwoong, Kim, Taejoon, Lee, Jang Ho, Cho, Kyoung Sang, Kang, Lin-Woo
• Format: Journal Article
• Language: English
• Published: Korea (South) Korean Society for Biochemistry and Molecular Biology 30-09-2022; 생화학분자생물학회
• Subjects: Amines; Amino Acids - metabolism; Catalysis; Contributed Mini Review; Phosphates; Pyridoxal Phosphate - chemistry; Pyridoxal Phosphate - metabolism; 화학
• ISSN: 1976-6696; 1976-670X
• DOI: 10.5483/BMBRep.2022.55.9.090

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. [BMB Reports 2022; 55(9): 439-446].