2jgt
From Proteopedia
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LOW RESOLUTION STRUCTURE OF SPT
Overview
Sphingolipid biosynthesis commences with the condensation of L-serine and palmitoyl-CoA to produce 3-ketodihydrosphingosine (KDS). This reaction is catalysed by the PLP-dependent enzyme serine palmitoyltransferase (SPT; EC 2.3.1.50), which is a membrane-bound heterodimer (SPT1/SPT2) in eukaryotes such as humans and yeast and a cytoplasmic homodimer in the Gram-negative bacterium Sphingomonas paucimobilis. Unusually, the outer membrane of S. paucimobilis contains glycosphingolipid (GSL) instead of lipopolysaccharide (LPS), and SPT catalyses the first step of the GSL biosynthetic pathway in this organism. We report here the crystal structure of the holo-form of S. paucimobilis SPT at 1.3 A resolution. The enzyme is a symmetrical homodimer with two active sites and a monomeric tertiary structure consisting of three domains. The PLP cofactor is bound covalently to a lysine residue (Lys265) as an internal aldimine/Schiff base and the active site is composed of residues from both subunits, located at the bottom of a deep cleft. Models of the human SPT1/SPT2 heterodimer were generated from the bacterial structure by bioinformatics analysis. Mutations in the human SPT1-encoding subunit have been shown to cause a neuropathological disease known as hereditary sensory and autonomic neuropathy type I (HSAN1). Our models provide an understanding of how these mutations may affect the activity of the enzyme.
About this Structure
2JGT is a Single protein structure of sequence from Sphingomonas paucimobilis. Active as Serine C-palmitoyltransferase, with EC number 2.3.1.50 Full crystallographic information is available from OCA.
Reference
The structure of serine palmitoyltransferase; gateway to sphingolipid biosynthesis., Yard BA, Carter LG, Johnson KA, Overton IM, Dorward M, Liu H, McMahon SA, Oke M, Puech D, Barton GJ, Naismith JH, Campopiano DJ, J Mol Biol. 2007 Jul 27;370(5):870-86. Epub 2007 May 10. PMID:17559874
Page seeded by OCA on Thu Feb 21 18:03:06 2008
Categories: Serine C-palmitoyltransferase | Single protein | Sphingomonas paucimobilis | Barton, G J. | Campopiano, D J. | Carter, L G. | Dorward, M. | Johnson, K A. | Liu, H. | Mcmahon, S A. | Naismith, J H. | Oke, M. | Overton, I M. | Puech, D. | Yard, B A. | Plp | Pyridoxal phosphate | Serine palmitoyl transferase | Sphingolipid | Spt | Sspf | Transferase