Disease relevance of PMI40

• The heterologous expression of the PMI 1 gene at levels up to 45% of total cell protein in E. coli leads to partitioning of the enzyme between the soluble and particulate fractions [1].
• Surprisingly, in view of the large differences between Pseudomonas aerugenosa and Saccharomyces cerevisiae PMI, the human and C. albicans enzymes are almost identical [2].

High impact information on PMI40

• The lipid moieties of both CP1 and CP2 can be removed by mild alkaline hydrolysis although the protein-bound GPI anchors made by the pmi40 cells under identical labeling conditions contain mild base resistant ceramides [3].
• Phosphomannose isomerase (PMI) catalyses the reversible isomerization of fructose-6-phosphate (F6P) and mannose-6-phosphate (M6P) [4].
• Deletion of the PMI40 coding sequence results in a strain requiring D-mannose for growth [5].
• The 48.2-kDa protein predicted to be encoded by PMI40 contains amino acid sequences corresponding to those of internal peptides derived from purified S. cerevisiae PMI [5].
• The PMI40 gene is located on chromosome V, and its transcription is increased 12-fold when cells are grown on D-mannose as sole carbon source instead of D-glucose [5].

Chemical compound and disease context of PMI40

• We therefore purified PMI from E. coli and showed that this enzyme is not sensitive to inactivation by iodoacetate [6].

Biological context of PMI40

• Phosphomannose isomerase (PMI40) catalyzes the conversion between fructose 6-phosphate and mannose 6-phosphate and thus connects glycolysis, i.e. energy production and GDP-mannose biosynthesis or cell wall synthesis in Saccharomyces cerevisiae [7].
• We have previously described a temperature-sensitive pmi40-1 mutant of Saccharomyces cerevisiae which is defective in glycosylation and secretion because of a thermolabile phosphomannose isomerase (PMI) activity [5].
• Inactivation of PMI at the restrictive temperature of 37 degrees C prevents synthesis of the GDP-mannose and dolichol-phosphate-mannose required for a number of critical mannosyl transfer reactions and results in cell death [5].
• Identification and characterization of the Cryptococcus neoformans phosphomannose isomerase-encoding gene, MAN1, and its impact on pathogenicity [8].
• Phosphomannose isomerase from Saccharomyces cerevisiae contains two inhibitory metal ion binding sites [9].

Associations of PMI40 with chemical compounds

• After PMI40 deletion (pmi(-)) the cells were viable only if fed with extracellular mannose and glucose [7].
• The iodoacetate is presumably inhibiting PMI by sterically blocking the mannose 6-phosphate binding site [6].
• However, metals such as zinc and cadmium, which are reversible, competitive inhibitors for PMI, do not protect the enzyme against modification [6].

Other interactions of PMI40

• Sequencing and functional analysis of the Hansenula polymorpha genomic fragment containing the YPT1 and PMI40 genes [10].

References