Topic
Protoporphyrin IX
About: Protoporphyrin IX is a research topic. Over the lifetime, 2250 publications have been published within this topic receiving 65544 citations. The topic is also known as: PpIX.
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24 citations
TL;DR: By use of tritium labelled substrates, and h.p.l.c., it is shown that protoporphyrin-IX (1d) is formed from coproporphyr inogen-IIIvia a specific pathway involving harderopomorphyrinogen (2b) rather than its isomer (2c).
Abstract: By use of tritium labelled substrates, and h.p.l.c., it is shown that protoporphyrin-IX (1d) is formed from coproporphyrinogen-III (2a)via a specific pathway involving harderoporphyrinogen (2b) rather than its isomer (2c).
24 citations
TL;DR: The novel mechanistic insights obtained from this study present a new starting point for future rational design of more efficient PPO inhibitors based on the product-bound PPO structure.
Abstract: Protoporphyrinogen IX oxidase (PPO; EC 1.3.3.4) is an essential enzyme catalyzing the last common step in the pathway leading to heme and chlorophyll biosynthesis. Great interest in PPO inhibitors arises from both its significance to agriculture and medicine. However, the discovery of PPO inhibitors with ultrahigh potency and selectivity is hampered due to lack of structural and mechanistic understanding about the substrate recognition, which remains a longstanding question central in porphyrin biology. To understand the mechanism, a novel binding model of protogen (protoporphyrinogen IX, the substrate) was developed through extensive computational simulations. Subsequently, amino acid residues that are critical for protogen binding identified by computational simulations were substituted by mutagenesis. Kinetic analyses of these mutants indicated that these residues were critical for protogen binding. In addition, the calculated free energies of protogen binding with these mutants correlated well with the experimental data, indicating the reasonability of the binding model. On the basis of this novel model, the fundamental mechanism of substrate recognition was investigated by performing potential of mean force (PMF) calculations, which provided an atomic level description of conformational changes and pathway intermediates. The free energy profile revealed a feedback inhibition mechanism of proto (protoporphyrin IX, the product), which was also in agreement with experimental evidence. The novel mechanistic insights obtained from this study present a new starting point for future rational design of more efficient PPO inhibitors based on the product-bound PPO structure.
24 citations
TL;DR: The fluorescence quenching efficiencies upon addition of methyl viologen are 2.3 and 2.6 fold-higher than those of the partially photosensitizer-inserted proteins, respectively, indicating that the energy migration occurs within the proteins.
24 citations
TL;DR: It is shown that active Mg chelatase and Mg‐protoporphyrin IX methyltransferase can be coupled in E. coli extracts and co‐expression of the chlM gene together with thechlH‐I‐D construct yielded soluble protein extracts which converted protoporphyr in IX to Mg•protoporalin IX monomethyl ester without detectable accumulation of the Mg •protoprophyrin VIII intermediate.
24 citations