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Plasmid DNA Preparation> | … A gene coding for the zymogen form of CatK was purchased from GenScript and recloned into expression plasmid pPICZαA (Thermo Fisher) using XhoI and NotI restriction sites … | Get A Quote |
Cathepsin K (CatK) is a target for the treatment of osteoporosis, arthritis, and bone metastasis. Peptidomimetics with a cyanohydrazide warhead represent a new class of highly potent CatK inhibitors; however, their binding mechanism is unknown. We investigated two model cyanohydrazide inhibitors with differently positioned warheads: an azadipeptide nitrile and a 3-cyano-3-aza-β-amino acid . Crystal structures of their covalent complexes were determined with mature CatK as well as a zymogen-like activation intermediate of CatK. Binding mode analysis, together with quantum chemical calculations, revealed that the extraordinary picomolar potency of is entropically favoured by its conformational flexibility at t... More