2jg2

From Proteopedia

Revision as of 17:57, 18 December 2007

HIGH RESOLUTION STRUCTURE OF SPT WITH PLP INTERNAL ALDIMINE

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

2JG2 is a Single protein structure of sequence from Sphingomonas paucimobilis with MG as ligand. Active as Serine C-palmitoyltransferase, with EC number 2.3.1.50 Known structural/functional Site: . 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

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