Structural Insights into the Enzymatic Mechanism of Serine Palmitoyltransferase from Sphingobacterium multivorum

摘要: Serine palmitoyltransferase (SPT) is a key enzyme of sphingolipid biosynthesis and catalyses the pyridoxal 5'-phosphate (PLP)-dependent decarboxylative condensation reaction l-serine with palmitoyl-CoA to generate 3-ketodihydrosphingosine. The crystal structure SPT from Sphingobacterium multivorum GTC97 complexed was determined at 2.3 A resolution. electron density map showed Schiff base formation between PLP in crystal. Because hydrogen bond His138, orientation Calpha-H PLP-l-serine aldimine not perpendicular PLP-Schiff plane. This conformation unfavourable for alpha-proton abstraction by Lys244 expected stop aldimine. Structural modelling following intermediates indicated that His138 changes its partner carboxyl group carbonyl upon binding palmitoyl-CoA, making These model structures well explained observations on bacterial SPTs alpha-deprotonation occurs only presence palmitoyl-CoA. study provides structural evidence directly supports our proposed mechanism substrate synergism reaction.