2JG2

HIGH RESOLUTION STRUCTURE OF SPT WITH PLP INTERNAL ALDIMINE

2JG2 の概要

• エントリーDOI: 10.2210/pdb2jg2/pdb
• 関連するPDBエントリー: 2JGT
• 分子名称: SERINE PALMITOYLTRANSFERASE, PYRIDOXAL-5'-PHOSPHATE, MAGNESIUM ION, ... (4 entities in total)
• 機能のキーワード: spt, plp, sspf, transferase, sphingolipid, pyridoxal phosphate, serine palmitoyl transferase
• 由来する生物種: PSEUDOMONAS PAUCIMOBILIS
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 45604.33

構造登録者

Yard, B.A.,Carter, L.G.,Johnson, K.A.,Overton, I.M.,Mcmahon, S.A.,Dorward, M.,Liu, H.,Puech, D.,Oke, M.,Barton, G.J.,Naismith, J.H.,Campopiano, D.J. (登録日: 2007-02-07, 公開日: 2007-05-01, 最終更新日: 2025-04-09)

主引用文献

Yard, B.A.,Carter, L.G.,Johnson, K.A.,Overton, I.M.,Dorward, M.,Liu, H.,Mcmahon, S.A.,Oke, M.,Puech, D.,Barton, G.J.,Naismith, J.H.,Campopiano, D.J.
The Structure of Serine Palmitoyltransferase; Gateway to Sphingolipid Biosynthesis.
J.Mol.Biol., 370:870-, 2007

PubMed Abstract: 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.

PubMed: 17559874
DOI: 10.1016/J.JMB.2007.04.086

実験手法

X-RAY DIFFRACTION (1.3 Å)