2i2w | pdb_00002i2w
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| 2i2w, resolution 1.95Å | |||||||||||||
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| Sites: | AC1 | ||||||||||||
| Ligands: | GOL | ||||||||||||
| Gene: | gmhA, lpcA, tfrA, b0222 (Escherichia coli) | ||||||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||||||
Crystal Structure of Escherichia Coli Phosphoheptose Isomerase
Overview
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.
About this Structure
2I2W is a Single protein structure of sequence from Escherichia coli. Full crystallographic information is available from OCA.
Reference
Structure and Function of Sedoheptulose-7-phosphate Isomerase, a Critical Enzyme for Lipopolysaccharide Biosynthesis and a Target for Antibiotic Adjuvants., Taylor PL, Blakely KM, de Leon GP, Walker JR, McArthur F, Evdokimova E, Zhang K, Valvano MA, Wright GD, Junop MS, J Biol Chem. 2008 Feb 1;283(5):2835-45. Epub 2007 Dec 3. PMID:18056714
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