The Pyridoxal 5′-Phosphate (PLP)-Dependent Enzyme Serine Palmitoyltransferase (SPT): Effects of the Small Subunits and Insights from Bacterial Mimics of Human hLCB2a HSAN1 Mutations

Figure 1

Proposed SPT mechanism. (a) Transamination of internal aldimine by incoming L-serine to form PLP-L-serine external aldimine intermediate; (b) binding of palmitoyl-CoA causes conformational change and deprotonation of external aldimine by Lys265 to form quinonoid/carbanion intermediate; (c) quinonoid/carbanion attack of the thioester; (d) formation of β-keto acid and CoASH release; (e) release of CO₂ to form KDS product quinonoid; (f) reprotonation of KDS; (g) transamination to release KDS and restore the internal aldimine with PLP-bound to Lys265.