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Kicking off sphingolipid biosynthesis: structures of the serine palmitoyltransferase complex

Nature Structural & Molecular Biology volume 28, pages 229–231 (2021)Cite this article

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Structures of the human serine palmitoyltransferase complex reveal the overall assembly, regulatory mechanisms and substrate selectivity of this key enzyme in sphingolipid synthesis.

These works describe the intricate structure of the initiating and rate-limiting enzyme complex in sphingolipid biosynthesis, serine palmitoyltransferase (SPT) (Fig. 1). SPT is so named because of its action: the condensation of an amino acid (almost always serine) and a fatty-acyl CoA (almost always the 16-carbon fatty acid palmitate). The product of this reaction (3-ketodihydrosphingosine) is rapidly transformed in a series of reactions to yield ceramides, sphingomyelins, glycosphingolipids and sphingosines (Fig. 1). The enzyme contains pyridoxal-5′-phosphate (PLP), which cycles between an internal and external (with serine) aldimine to promote catalysis.

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Fig. 1: The sphingolipid metabolic pathway.
Fig. 2: Structure of the serine palmitoyltransferase complex.

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Acknowledgements

This work was supported by NIH R01HL131340 to B.W.

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  1. Department of Biochemistry and Molecular Biology, Virginia Commonwealth University School of Medicine, Richmond, VA, USA

    Binks W. Wattenberg

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Correspondence to Binks W. Wattenberg.

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Wattenberg, B.W. Kicking off sphingolipid biosynthesis: structures of the serine palmitoyltransferase complex. Nat Struct Mol Biol 28, 229–231 (2021). https://doi.org/10.1038/s41594-021-00562-0

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