THE HELICOBACTER-PYLORI UREC GENE CODES FOR A PHOSPHOGLUCOSAMINE MUTASE

The function of UreC, the product of a 1,335-bp-long open reading fram e upstream from the urease structural genes (ureAB) of Helicobacter py lori, was investigated. We present data showing that the ureC gene pro duct is a phosphoglucosamine mutase. D. Mengin-Lecreulx and J. van Hei jenoort (J. Biol. Chem. 271:32-39, 1996) observed that UreC is similar (43% identity) to the GlmM protein of Escherichia coli. Those authors showed that GlmM is a phosphoglucosamine mutase catalyzing interconve rsion of glucosamine-6-phosphate into glucosamine-l-phosphate, which i s subsequently transformed into UDP-N-acetylglucosamine. The latter pr oduct is one of the main cytoplasmic precursors of cell wall peptidogl ycan and outer membrane lipopolysaccharides. The present paper reports that, like its E. coli homolog glmM, the H. pylori ureC gene is essen tial for cell growth. It was known that growth of a lethal conditional glmM mutant of E. coli at a nonpermissive temperature can be restored in the presence of the ureC gene. We showed that complete complementa tion of the glmM mutant can be obtained with a plasmid overproducing U reC. The peptidoglycan content and the specific phosphoglucosamine mut ase activity of such a complemented strain were measured; these result s demonstrated that the ureC gene product functions as a phosphoglucos amine mutase. Homologs of the UreC and GlmM proteins were identified i n Haemophilus influenzae, Mycobacterium leprae, clostridium perfringen s, Synechocystis sp. strain PCC6803, and Methanococcus jannaschii. Sig nificant conservation of the amino acid sequence of these proteins in such diverse organisms suggests a very ancient common ancestor for the genes and defines a consensus motif for the phosphoglucosamine mutase active site. We propose renaming the H. pylori ureC gene the glmM gen e.