Identification of novel allosteric regulators of human-erythrocyte pyruvate kinase.

摘要: Erythrocyte pyruvate kinase (PK) is an important glycolytic enzyme, and manipulation of its regulatory behavior by allosteric modifiers interest for medicinal purposes. Human-erythrocyte PK was expressed in Rosetta cells purified on Ni-NTA column. A search the small-molecules database National Cancer Institute (NCI), using UNITY software, led to identification several compounds with similar pharmacophores as fructose-1,6-bisphosphate (FBP), natural activator human kinases. The were subsequently docked into FBP binding site programs FlexX GOLD, their interactions protein analyzed energy-scoring function HINT. Seven promising candidates, 1-7, obtained from NCI, subjected kinetics analysis, which revealed both activators inhibitors R-isozyme (R-PK). effectors discovered this study could prove be lead developing medications treatment hemolytic anemia, sickle-cell hypoxia-related diseases, other disorders arising erythrocyte malfunction.