Precision medicine gives individuals tailored medical treatment, with the genotype determining the therapeutic strategy, the appropriate dosage, and the likelihood of benefit or toxicity. Cytochrome P450 (CYP) enzyme families 1, 2, and 3 play a pivotal role in eliminating most drugs. Factors that affect CYP function and expression have a major impact on treatment outcomes.
View Article and Find Full Text PDFBacterial glycoside hydrolase 1 (GH1) enzymes with 6-phospho-β-galactosidase and 6-phospho-β-glucosidase activities have the important task of releasing phosphorylated and nonphosphorylated monosaccharides into the cytoplasm. Curiously, dual 6-phospho-β-galactosidase/6-phospho-β-glucosidase (dual-phospho) enzymes have broad specificity and are able to hydrolyze galacto- and gluco-derived substrates. This study investigates the structure and substrate specificity of a GH family 1 enzyme from , hereafter known as BglC.
View Article and Find Full Text PDFIn bacteria, mono- and disaccharides are phosphorylated during the uptake processes through the vastly spread transport system phosphoenolpyruvate-dependent phosphotransferase. As an initial step in the phosphorylated disaccharide metabolism pathway, 6-phospho-β-glucosidases and 6-phospho-β-galactosidases play a crucial role by releasing phosphorylated and nonphosphorylated monosaccharides. However, structural determinants for the specificity of these enzymes still need to be clarified.
View Article and Find Full Text PDFUnderstanding molecular mechanisms underlying the complexity of allosteric regulationin proteins has attracted considerable attention in drug discovery due to the benefits and versatilityof allosteric modulators in providing desirable selectivity against protein targets while minimizingtoxicity and other side effects. The proliferation of novel computational approaches for predictingligand-protein interactions and binding using dynamic and network-centric perspectives has ledto new insights into allosteric mechanisms and facilitated computer-based discovery of allostericdrugs. Although no absolute method of experimental and allosteric drug/site discoveryexists, current methods are still being improved.
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