Mechanistic insights into the substrate recognition of PPO: Toward the rational design of effective inhibitors

摘要

PPO inhibitor design is undergoing a radical transition from laborious to more efficient ways based on the detailed understanding of protein structures and mechanisms in various species [i]. Development of structure-based design methods and understanding of relevant mechanistic studies play a key role in this transition [2-4]. Why are PPO inhibitors important? PPO is the last common enzyme for the biosynthesis of heme and chlorophyll, catalyzing the oxidation of protoporphyrinogen-IX to protoporphyrin-IX [5]. The inhibition or functional loss of PPO is more than merely blocking the production of heme and chlorophyll. When the enzyme is inhibited, the substrate protoporphyrinogen-IX will accumulate in the cytoplasm and will be slowly oxidized in the mitochondrion and chloro-plast to produce protoporphyrin-IX.