Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.5.1.52 (PNGase F)
 1,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A cytoplasmic peptide:N-glycanase has been implicated in the proteasomal degradation of newly synthesized misfolded glycoproteins exported from the endoplasmic reticulum. The gene encoding this enzyme (Png1p) has been identified in yeast. Based on sequence analysis, Png1p was classified as a member of the 'transglutaminase-like superfamily' that contains a putative catalytic triad of amino acids (cysteine, histidine, and aspartic acid). More recent studies in yeast indicate that Png1p can bind to the 26S proteasome through its interaction with the DNA repair protein Rad23p. A mouse homologue of Png1p (mPng1p) bound not only to the Rad23 protein, but also to various proteins related to ubiquitin and/or the proteasome through an extended amino-terminal domain. This NH2 terminus of mPng1p, which is not found in yeast, contains a PUB domain predicted to be involved in the ubiquitin-related pathway. This review will focus on the primary structure and potential functions of the cytoplasmic PNGases.
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PMID:Cytoplasmic peptide:N-glycanase (PNGase) in eukaryotic cells: occurrence, primary structure, and potential functions. 1197 27

Yeast peptide: N-glycanase (PNGase) is involved in the proteasomal degradation of misfolded glycoproteins where it interacts with the DNA repair protein Rad23 as first detected in a yeast two-hybrid assay and subsequently confirmed by biochemical in vivo analyses. Limited proteolysis of PNGase with trypsin led to the removal of both an N-terminal and a C-terminal stretch. Based on these truncations the N-terminal region of yeast PNGase was identified as being responsible for binding to Rad23. Secondary structure predictions of this region suggest that it is composed of a single, solvent-exposed alpha-helix. The interaction between PNGase and Rad23 was studied using surface plasmon resonance revealing an equilibrium binding constant of approximately 2.5 microM. The oligomeric nature of Rad23 was also investigated using sedimentation equilibrium analysis. Although Rad23 exists as a dimer in solution, the monomeric form of Rad23 associates with a PNGase monomer in a 1:1 stoichiometric ratio.
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PMID:The N-terminus of yeast peptide: N-glycanase interacts with the DNA repair protein Rad23. 1535 14

In eukaryotes, misfolded proteins must be distinguished from correctly folded proteins during folding and transport processes by quality control systems. Yeast peptide:N-glycanase (yPNGase) specifically deglycosylates the denatured form of N-linked glycoproteins in the cytoplasm and assists proteasome-mediated glycoprotein degradation by forming a complex with 26S proteasome through DNA repair protein, yRad23. Here, we describe the crystal structures of a yPNGase and XPC-binding domain of yRad23 (yRad23XBD, residues 238-309) complex and of a yPNGase-yRad23XBD complex bound to a caspase inhibitor, Z-VAD-fmk. yPNGase is formed with three domains, a core domain containing a Cys-His-Asp triad, a Zn-binding domain, and a Rad23-binding domain. Both N- and C-terminal helices of yPNGase interact with yRad23 through extensive hydrophobic interactions. The active site of yPNGase is located in a deep cleft that is formed with residues conserved in all PNGase members, and three sugar molecules are bound to this cleft. Complex structures in conjunction with mutational analyses revealed that the walls of the cleft block access to the active site of yPNGase by native glycoprotein, whereas the cleft is sufficiently wide to accommodate denatured glycoprotein, thus explaining the specificity of PNGase for denatured substrates.
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PMID:Structure of a peptide:N-glycanase-Rad23 complex: insight into the deglycosylation for denatured glycoproteins. 1596 83