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l-Penicillamine is a mechanism-based inhibitor of serine palmitoyltransferase by forming a pyridoxal-5′-phosphate-thiazolidine adduct†‡
Jonathan Lowther,Ashley E. Beattie,Pat R. R. Langridge-Smith,David J. Clarke,Dominic J. Campopiano
MedChemComm Pub Date : 04/17/2012 00:00:00 , DOI:10.1039/C2MD20020A
Abstract

Serine palmitoyltransferase (SPT) catalyses the first committed step of de novo sphingolipid biosynthesis. The bacterial SPT homologue from Sphingomonas paucimobilis is a homodimeric enzyme that contains an essential pyridoxal-5′-phosphate (PLP) cofactor bound to each subunit. Inhibitors of SPT are useful blockers of sphingolipid biosynthesis. Here we use UV-vis spectroscopy, enzyme kinetics and mass spectrometry to investigate inhibition of SPT by penicillamine (Pen), a drug with a range of useful medicinal applications.

Graphical abstract: l-Penicillamine is a mechanism-based inhibitor of serine palmitoyltransferase by forming a pyridoxal-5′-phosphate-thiazolidine adduct
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