Researchers Uncover Atomic Structure of Enzyme Linked to Important Lipid Mediator

For the scientific community, it’s been a long time coming - but now for the first time, the atomic structure of the enzyme, sphinogosine kinase 1, SphK1, responsible for an important potent lipid mediator, sphingosine-1-phosphate, has been uncovered by a research team at Amgen in San Francisco.

Sarah Spiegel, Ph.D., an internationally renowned researcher and professor and chair of the Department of Biochemistry and Molecular Biology in the Virginia Commonwealth University School of Medicine, together with Santiago Lima, Ph.D., postdoctoral fellow in the Department of Biochemistry and Molecular Biology, have co-authored an article on the topic for the Previews section of the Cell Press journal, Structure.

In their expert commentary, Spiegel and Lima discuss how the newly discovered atomic structure of sphingosine-1-phosphate will expand mechanistic understanding of the molecule significantly. The molecule itself was originally discovered by Spiegel in the mid-1990s and has been found to play a role in cancer progression, inflammation and cardiovascular disease.

For many years, cell biologists, including Spiegel and her colleagues, have investigated how sphingosine-1-phosphate, S1P, and sphinogosine kinase 1, SphK1, function and the molecular pathways they are involved with. But its precise structure has remained unclear until now.

“The sturctures provide a vital baseline from which to generate predictions and targeted modifications that further probe the many nuances of functional elements in SphK1 activity and regulation,” wrote Spiegel and Lima.

“These findings will provide us with molecular tools to understand the functions of this important enzyme as well as development of new drugs that target it in cancer and inflammation,” said Spiegel.

Spiegel, who is also the program co-leader of the Cancer Cell Biology Program at the VCU Massey Cancer Center and the Mann T. and Sara D. Lowry Professor of Oncology, has received multiple grants from the National Institutes of Health to continuously fund her research for nearly 20 years. In 2003, she was awarded a National Institutes of Health MERIT award totaling nearly $2.1 million to continue her research on S1P. The award is given to investigators who have demonstrated superior competence and productivity.