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Molecular Modeling of the Three‐Dimensional Structure of Human Sphingomyelin Synthase
Author(s) -
Zhang Ya,
Lin Fu,
Deng Xiaodong,
Wang Renxiao,
Ye Deyong
Publication year - 2011
Publication title -
chinese journal of chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.28
H-Index - 41
eISSN - 1614-7065
pISSN - 1001-604X
DOI - 10.1002/cjoc.201180282
Subject(s) - sphingomyelin , chemistry , ceramide , homology modeling , biochemistry , stereochemistry , computational biology , enzyme , apoptosis , biology , membrane
Sphingomyelin synthase (SMS) produces sphingomyelin and diacylglycerol from ceramide and phosphatidylcholine. It plays an important role in cell survival and apoptosis, inflammation, and lipid homeostasis, and therefore has been noticed in recent years as a novel potential drug target. In this study, we combined homology modeling, molecular docking, molecular dynamics simulation, and normal mode analysis to derive a three‐dimensional structure of human sphingomyelin synthase ( h SMS1) in complex with sphingomyelin. Our model provides a reasonable explanation on the catalytic mechanism of h SMS1. It can also explain the high selectivity of h SMS1 towards phosphocholine and sphingomyelin as well as some other known experimental results about h SMS1. Moreover, we also derived a complex model of D609, the only known small‐molecule inhibitor of h SMS1 so far. Our h SMS1 model may serve as a reasonable structural basis for the discovery of more effective small‐molecule inhibitors of h SMS1.