An Oxygen Sensation: Progress in Macromolecule Hydroxylation Triggered by the Elucidation of Cellular Oxygen Sensing

The 2019 Nobel Prize in Physiology or Medicine honours three scientists that devoted their careers to pursuing an audacious basic science question: by what mechanisms do animals sense oxygen, and how can cells adapt to a lack of oxygen? The identification of the human hypoxia inducible factor pathway has enabled new approaches for the therapy of related diseases including cancer, cardiovascular disease, anaemia, and stroke. The intricate molecular details of oxygen sensing broadened interest in the family of iron‐ and 2‐oxoglutarate‐dependent oxygenases known from elaborate natural product chemistry, and catalysed major progress in macromolecule hydroxylation. The laureates’ work enables numerous avenues for molecular scientists, from C?H activation chemistry to PROTAC technology, medicinal chemistry, and epigenetics.     

Discrimination of enzyme–substrate complexes by reactivity using the electron density analysis: peptide bond hydrolysis by the matrix metalloproteinase-2

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