Interdiscip Cardiovasc Thorac Surg
June 2024
Objectives: The gold standard metric for centre-level performance in orthotopic heart transplantation (OHT) is 1-year post-OHT survival. However, it is unclear whether centre performance at 1 year is predictive of longer-term outcomes. This study evaluated factors impacting longer-term centre-level performance in OHT.
View Article and Find Full Text PDFHuman UDP-glucose dehydrogenase (hUGDH) oxidizes uridine diphosphate (UDP)-glucose to UDP-glucuronic acid, an essential substrate in the phase II metabolism of drugs. The activity of hUGDH is controlled by an atypical allosteric mechanism in which the feedback inhibitor UDP-xylose competes with the substrate for the active site and triggers a buried allosteric switch to produce an inactive complex (E). Previous comparisons with a nonallosteric UGDH identified six large-to-small substitutions that produce packing defects in the protein core and provide the conformational flexibility necessary for the allosteric transition.
View Article and Find Full Text PDFProtein structures are dynamic and can explore a large conformational landscape. Only some of these structural substates are important for protein function (such as ligand binding, catalysis and regulation). How evolution shapes the structural ensemble to optimize a specific function is poorly understood.
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