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

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Pyridoxal 5’-phosphate (PLP)-dependent enzymes are ubiquitous,catalyzing various biochemical reactions of approximately 4%of all classified enzymatic activities. They transform amines andamino acids into important metabolites or signaling moleculesand are important drug targets in many diseases. In the crystalstructures of PLP-dependent enzymes, organic cofactor PLPshowed diverse conformations depending on the catalytic step. The conformational change of PLP is essential in the catalyticmechanism. In the study, we review the sophisticated catalyticmechanism of PLP, especially in transaldimination reactions. Most drugs targeting PLP-dependent enzymes make a covalentbond to PLP with the transaldimination reaction. A detailedunderstanding of organic cofactor PLP will help develop a newdrug against PLP-dependent enzymes.

Abstract

Pyridoxal 5’-phosphate (PLP)-dependent enzymes are ubiquitous,catalyzing various biochemical reactions of approximately 4%of all classified enzymatic activities. They transform amines andamino acids into important metabolites or signaling moleculesand are important drug targets in many diseases. In the crystalstructures of PLP-dependent enzymes, organic cofactor PLPshowed diverse conformations depending on the catalytic step. The conformational change of PLP is essential in the catalyticmechanism. In the study, we review the sophisticated catalyticmechanism of PLP, especially in transaldimination reactions. Most drugs targeting PLP-dependent enzymes make a covalentbond to PLP with the transaldimination reaction. A detailedunderstanding of organic cofactor PLP will help develop a newdrug against PLP-dependent enzymes.

참고문헌 (63)

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