Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:5.4.2.8 (phosphomannomutase)
 238 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The low activity levels of the four GDP-D-mannuronic acid-forming enzymes, even in highly alginate-producing strains of Pseudomonas aeruginosa, have made it difficult to compare enzyme activities accompanying the loss/acquisition of mucoidy. Using optimized conditions, we compared the specific activity of these enzymes in three different mucoid P. aeruginosa cystic fibrosis isolates, in their nonmucoid spontaneous variants, and in mucoid variants that emerged during extended incubation of these nonmucoid forms in acetamide broth. A correlation was established between the promptness of emergence of the mucoid forms and the differing sensitivity to nutrient-limitation-induced death of the nonmucoid compared with the isogenic mucoid population. Consistent with the undetectable levels of algD mRNA in nonmucoid forms and with the concept that the step catalyzed by the algD-encoded GDP-mannose dehydrogenase (GMD) is a key step in control of the alginate pathway, GMD activity was undetectable or showed negligible values in nonmucoid variants and correlated with alginate production. However, phosphomannose isomerase (PMI), phosphomannomutase (PMM), and GDP-mannose pyrophosphorylase (GMP) activities in the nonmucoid forms were only slightly (40-70%) below the values in the mucoid forms. Nevertheless, no transcripts homologous to algA (encoding a bifunctional enzyme that possesses both PMI and GMP activities) were detected in the nonmucoid form, and the levels of algC (encoding PMM) transcripts, although detectable in the nonmucoid variants, were, in general, much higher in the mucoid forms. These apparently intriguing observations were cleared up by the identification of two algA functional homologues in P. aeruginosa, recently reported by others, and by the identification of one algC homologue, in contig225 of the PAO1 genome sequence, defining a polypeptide with a deduced amino acid sequence that showed significant homology with that of enzymes of the phosphohexomutase family found in databases. Results are also consistent with the requirement of PMI, GMP and PMM activities for the supply of GDP-D-mannose to (at least) A-band lipopolysaccharide synthesis, while GMD channels this precursor into the alginate pathway.
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PMID:Pattern of changes in the activity of enzymes of GDP-D-mannuronic acid synthesis and in the level of transcription of algA, algC and algD genes accompanying the loss and emergence of mucoidy in Pseudomonas aeruginosa. 1020 66

The alpha-D-phosphohexomutase superfamily is composed of four related enzymes that catalyze a reversible, intramolecular phosphoryl transfer on their sugar substrates. The enzymes in this superfamily play important and diverse roles in carbohydrate metabolism in organisms from bacteria to humans. Recent structural and mechanistic studies of one member of this superfamily, phosphomannomutase/phosphoglucomutase (PMM/PGM) from Pseudomonas aeruginosa, have provided new insights into enzyme mechanism and substrate recognition. Here we use sequence-sequence and sequence-structure comparisons via evolutionary trace analysis to examine 71 members of the alpha-D-phosphohexomutase superfamily. These analyses show that key residues in the active site, including many of those involved in substrate contacts in the P. aeruginosa PMM/PGM complexes, are conserved throughout the enzyme family. Several important regions show class-specific differences in sequence that appear to be correlated with differences in substrate specificity exhibited by subgroups of the family. In addition, we describe the translocation of a 20-residue segment containing the catalytic phosphoserine of phosphoacetylglucosamine mutase, which uniquely identifies members of this subgroup.
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PMID:Evolutionary trace analysis of the alpha-D-phosphohexomutase superfamily. 1523 32

The Toxoplasma gondii genome project has revealed two putative isoforms (TgPGM-I and TgPGM-II) of alpha-phosphoglucomutase (EC 5.4.2.2). We obtained recombinant proteins of these isoforms from the Beverley strain of T. gondii and characterized their properties, particularly the kinetic properties of these isoforms. The specific activities of TgPGM-I and TgPGM-II for alpha-D-glucose 1-phosphate were 338+/-9 and 84+/-6micromol/min/mg protein, respectively, at 37 degrees C under optimal conditions. The Kcat and Km values of TgPGM-I were 398+/-11/s and 0.19+/-0.03mM and those for TgPGM-II were 93+/-7/s and 3.53+/-0.91mM, respectively, for alpha-d-glucose 1-phosphate. Magnesium ions were the most effective divalent cations for both the enzyme activities. The maximum activities of both the enzymes were obtained in the presence of more than 0.2mM alpha-D-glucose 1,6-bisphosphate. Although both enzymes were attached to the alpha-phosphohexomutase superfamily, amino acid sequence homology between TgPGM-I and TgPGM-II showed very low overall identity (25%). No alpha-phosphomannomutase (EC 5.4.2.8) activity was detected for either enzyme. The data indicated that TgPGM-I, but not TgPGM-II, may play an important role in alpha-D-glucose 6-phosphate production.
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PMID:Characterization of alpha-phosphoglucomutase isozymes from Toxoplasma gondii. 2015 38