Disease relevance of PNG1

• Furthermore, the deglycosylation efficiency of recombinant Png1p from E. coli was investigated with respect to the substrate conformation in vitro [1].

High impact information on PNG1

• The Png1-Rad23 complex regulates glycoprotein turnover [2].
• The PNG1 gene was mapped to the left arm of chromosome XVI by genetic approaches and its open reading frame was identified [3].
• Sequencing of expressed sequence tag clones revealed that Png1p is highly conserved in a wide variety of eukaryotes including mammals, suggesting that the enzyme has an important function [3].
• Subcellular localization studies indicate that Png1p is present in the nucleus as well as the cytosol [3].
• The inhibition was found to be through covalent binding of the carbohydrate to a single Cys residue on Png1, and the binding was highly selective [4].

Biological context of PNG1

• Peptide:N-glycanase, encoded by the PNG1 gene, was found to be required for the generation of a large proportion of yeast fOS during, and soon after, protein glycosylation [5].
• The Png1p-Rad23p complex was shown to be distinct from the well established DNA repair complex, Rad4p-Rad23p [6].
• Point mutations of these residues in Png1p resulted in complete loss in activity, consistent with a role for each in catalyzing deglycosylation of glycoproteins [7].
• The substrate specificity of Png1 is admirably suited for this task [8].
• The recently uncovered complete genome sequence of Arabidopsis thaliana prompted us to search for the protein homologue of Png1p in this organism [9].

Anatomical context of PNG1

• The only known in vivo substrates of Png1 are aberrant glycoproteins that originate in the endoplasmic reticulum, and arrive in the cytoplasm for proteasomal degradation [8].
• In the present study, a recombinant, yeast peptide:N-glycanase, Png1p, was expressed in Escherichia coli as inclusion bodies and was purified, refolded and characterized [1].

Associations of PNG1 with chemical compounds

• PNG1 may be required for efficient proteasome-mediated degradation of a misfolded glycoprotein [3].
• When ribonuclease B (RNase B) was denatured at 60-65 degrees C or by 40-60 mM dithiothreitol, indicated by its obvious structural change and sharpest activity change, its deglycosylation by Png1p was most prominent [1].

Physical interactions of PNG1

• More recent studies in yeast indicate that Png1p can bind to the 26S proteasome through its interaction with the DNA repair protein Rad23p [10].

Other interactions of PNG1

• Free-oligosaccharide control in the yeast Saccharomyces cerevisiae: roles for peptide:N-glycanase (Png1p) and vacuolar mannosidase (Ams1p) [5].
• Rad23 provides a link between the Png1 deglycosylating enzyme and the 26 S proteasome in yeast [6].

Analytical, diagnostic and therapeutic context of PNG1

• In this study we have investigated the structure-function relationship of Png1p by site-directed mutagenesis [7].
• Yeast peptide:N-glycanase (Png1p; PNGase), a deglycosylation enzyme involved in the proteasome dependent degradation of proteins, has been reported to be a member of the transglutaminase superfamily based on sequence alignment [7].

References