Work of Diana Campelo selected for oral presentation

Michel Kranendonk, Francisco Esteves and Diana Campelo, from the Xenobiotics Metabolism lab, recently attended the 20th International Conference on Cytochrome P450, that occurred in Düsseldorf, Germany.
This is a worldwide meeting that started in 1976 and occurs now biannually rotating around the world.

The work of Diana Campelo was selected for an oral presentation which was very well received by the P450 scientific community. Diana focuses her work on the conformational equilibrium of CPR (NADPH-cytochrome P450 reductase), between the locked and unlocked states for its electron-transfer function. In her study, Diana Campelo showed that specific residues of the hinge segment control the conformational equilibrium of CPR protein and its electron-transfer function. Congratulations!


The work presented at this conference on Cytochrome P450 by Diana Campelo is part of the work developed under her PhD project, named "Genetic variants of NADPH cytochrome P450 oxidoreductase: mapping structural protein elements responsible for its gated electron transfer function".

Short summary of Diana Campelo's work: Short summary of Diana Campelo's work: Human multi-domain NADPH cytochrome P450 reductase (CPR) is the obligatory electron supplier for mammalian microsomal cytochrome P450 (CYP) but also of other enzymes such as heme oxygenase (HO) and squalene mono-oxygenase (SQMO). CPR’s interactions with these enzymes play a key role in their activity and thus in the metabolism of therapeutic drugs, xenobiotics, steroid hormones, but also in sterol metabolism and heme degradation. Experimental data indicated that CPR exists in a conformational equilibrium between open and closed conformations throughout its electron transfer (ET) function. However, there is a scarcity in data concerning the structural protein features of CPR, controlling these open-closed dynamics. Detailed knowledge on the mechanism of CPR electron-transfer in sustaining activity of its protein partners is of importance, not only for elucidating the malfunction of human genetic CPR variants but also to obtain more detailed insights on the role of CPR’s gated ET on the molecular mechanism of CYP functioning, the focus of Diana’s work. The latter is of general relevance for pharmacokinetic/toxicokinetic understanding of therapeutic drug and steroid metabolism, but also for other physiological relevant processes such as sterol and heme homeostasis.

To learn more about the Lab of Michel Kranendonk please visit the dedicated website using this link.

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