3BJZ

Crystal structure of Pseudomonas aeruginosa phosphoheptose isomerase

Summary for 3BJZ

• Entry DOI: 10.2210/pdb3bjz/pdb
• Related: 1X92 2I22 2I2W
• Descriptor: Phosphoheptose isomerase, SULFATE ION, CHLORIDE ION, ... (4 entities in total)
• Functional Keywords: sis domain, alpha/beta protein, lipopolysaccharide biosynthesis, psi, protein structure initiative, midwest center for structural genomics, mcsg, carbohydrate metabolism, cytoplasm, isomerase
• Biological source: Pseudomonas aeruginosa PAO1
• Cellular location: Cytoplasm (By similarity): Q9HVZ0
• Total number of polymer chains: 4
• Total formula weight: 87871.60

Authors

Walker, J.R.,Evdokimova, E.,Kudritska, M.,Osipiuk, J.,Joachimiak, A.,Savchenko, A.,Midwest Center for Structural Genomics (MCSG) (deposition date: 2007-12-05, release date: 2007-12-18, Last modification date: 2024-11-06)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.4 Å)