A5051635085- Pharmacogenetics and Drug Metabolism
- Drug Transport and Resistance Mechanisms
- Computational Drug Discovery Methods
- Receptor Mechanisms and Signaling
- Estrogen and related hormone effects
- Steroid Chemistry and Biochemistry
- Pharmacological Effects and Toxicity Studies
Universidade Nova de Lisboa
2018-2020
NADPH cytochrome P450 oxidoreductase (CPR) is the obligatory electron supplier in sustaining activity of microsomal (CYP). The variant nature isoform specific proximal interface CYPs implies that CPR capable multiple degenerated interactions with for transfer, through different binding mechanisms, which are still not well understood. Recently, we showed dynamics allows formation open conformers can be sampled by its structurally diverse redox partners a CYP-isoform dependent manner. To...
NADPH-cytochrome P450 reductase (CPR) is a redox partner of microsomal cytochrome P450s and prototype the diflavin family. CPR contains 3 distinct functional domains: FMN-binding domain (acceptor reduction), linker (hinge), connecting/FAD (NADPH oxidation). It has been demonstrated that mechanism exhibits an important step in which it switches from compact, closed conformation (locked state) to ensemble open conformations (unlocked state), latter enabling electron transfer partners. The...
NADPH-cytochrome P450 reductase (CPR) is the unique redox partner of microsomal cytochrome P450s (CYPs). CPR exists in a conformational equilibrium between open and closed conformations throughout its electron transfer (ET) function. Previously, we have shown that electrostatic flexibility properties hinge segment are critical for ET. Three mutants human were studied (S243P, I245P R246A) combined with representative drug-metabolizing CYPs (isoforms 1A2, 2A6 3A4). To probe effect these...