3BJZ

Crystal structure of Pseudomonas aeruginosa phosphoheptose isomerase

3BJZ の概要

• エントリーDOI: 10.2210/pdb3bjz/pdb
• 関連するPDBエントリー: 1X92 2I22 2I2W
• 分子名称: Phosphoheptose isomerase, SULFATE ION, CHLORIDE ION, ... (4 entities in total)
• 機能のキーワード: sis domain, alpha/beta protein, lipopolysaccharide biosynthesis, psi, protein structure initiative, midwest center for structural genomics, mcsg, carbohydrate metabolism, cytoplasm, isomerase
• 由来する生物種: Pseudomonas aeruginosa PAO1
• 細胞内の位置: Cytoplasm (By similarity): Q9HVZ0
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 87871.60

構造登録者

Walker, J.R.,Evdokimova, E.,Kudritska, M.,Osipiuk, J.,Joachimiak, A.,Savchenko, A.,Midwest Center for Structural Genomics (MCSG) (登録日: 2007-12-05, 公開日: 2007-12-18, 最終更新日: 2024-11-06)

主引用文献

Taylor, P.L.,Blakely, K.M.,de Leon, G.P.,Walker, J.R.,McArthur, F.,Evdokimova, E.,Zhang, K.,Valvano, M.A.,Wright, G.D.,Junop, M.S.
Structure and Function of Sedoheptulose-7-phosphate Isomerase, a Critical Enzyme for Lipopolysaccharide Biosynthesis and a Target for Antibiotic Adjuvants.
J.Biol.Chem., 283:2835-2845, 2008

PubMed Abstract: The barrier imposed by lipopolysaccharide (LPS) in the outer membrane of Gram-negative bacteria presents a significant challenge in treatment of these organisms with otherwise effective hydrophobic antibiotics. The absence of L-glycero-D-manno-heptose in the LPS molecule is associated with a dramatically increased bacterial susceptibility to hydrophobic antibiotics and thus enzymes in the ADP-heptose biosynthesis pathway are of significant interest. GmhA catalyzes the isomerization of D-sedoheptulose 7-phosphate into D-glycero-D-manno-heptose 7-phosphate, the first committed step in the formation of ADP-heptose. Here we report structures of GmhA from Escherichia coli and Pseudomonas aeruginosa in apo, substrate, and product-bound forms, which together suggest that GmhA adopts two distinct conformations during isomerization through reorganization of quaternary structure. Biochemical characterization of GmhA mutants, combined with in vivo analysis of LPS biosynthesis and novobiocin susceptibility, identifies key catalytic residues. We postulate GmhA acts through an enediol-intermediate isomerase mechanism.

PubMed: 18056714
DOI: 10.1074/jbc.M706163200

実験手法

X-RAY DIFFRACTION (2.4 Å)