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Functional And Structural Studies On The Neisseria Gonorrhoeae Gmha, The First Enzyme In The Glycero-Manno-Heptose Biosynthesis Pathways, Demonstrate A Critical Role In Lipooligosaccharide Synthesis And Gonococcal Viability, Igor H. Wierzbicki, Ryszard A. Zielke, Konstantin V. Korotkov, Aleksandra E. Sikora

Molecular and Cellular Biochemistry Faculty Publications

Sedoheptulose-7-phosphate isomerase, GmhA, is the first enzyme in the biosynthesis of nucleotide-activated-glycero-manno-heptoses and an attractive, yet underexploited, target for development of broad-spectrum antibiotics. We demonstrated that GmhA homologs in Neisseria gonorrhoeae and N. meningitidis (hereafter called GmhA_GC and GmhA_NM, respectively) were interchangeable proteins essential for lipooligosaccharide (LOS) synthesis, and their depletion had adverse effects on neisserial viability. In contrast, the Escherichia coli ortholog failed to complement GmhA_GC depletion. Furthermore, we showed that GmhA_GC is a cytoplasmic enzyme with induced expression at mid-logarithmic phase, upon iron deprivation and anaerobiosis, and conserved in contemporary gonococcal …