Computational study on human sphingomyelin synthase 1 (hSMS1)

摘要

Abstract Human sphingomyelin synthase 1 (hSMS1) is the last enzyme for sphingomyelin (SM) biosynthesis. It has been discovered that in different human tumor tissues the SM levels are lower compared to normal tissues and the activation of hSMS1, to restore the normal levels of SM, inhibits cell cycle proliferation of cancer cells. Since the importance of SM and other lipid metabolism genes in the malignant transformation, we decided to explore the hSMS1 mechanism of action. Enzymes capable to regulate the formation of lipids are therefore of paramount importance. Here we present a computational study on sphingomyelin synthases hSMS1. The full structure of the enzyme was obtained by means of homology and ab initio techniques. Further molecular dynamics and docking studies permitted to identify putative binding sites and to identify the key residues for binding. This article is part of a Special Issue entitled: Membrane Lipid Therapy: Drugs Targeting Biomembranes edited by Pablo V. Escribá. Graphical abstract Display Omitted Highlights ? The 3-dimensional structure of hSMS1 was obtained by means of homology and molecular dynamics ? The residence time of phosphocoline (PC) is shorter than sphingomyelin (SM) ? The hSMS1 binding site is extremely conserved and 3 amino acids are involved in the SM synthesis: Asp101, Arg220 and Asn358 ? The hydroxylation of PC increases the rate of conversion from PC into SM ]]>