Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.5.1.52 (
PNGase F
)
1,527
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Peptide
N-glycanase
removes N-linked oligosaccharides from misfolded glycoproteins as part of the endoplasmic reticulum-associated degradation pathway. This process involves the formation of a tight complex of peptide
N-glycanase
with Rad23 in yeast and the orthologous HR23 proteins in mammals. In addition to its function in endoplasmic reticulum-associated degradation, HR23 is also involved in DNA repair, where it plays an important role in damage recognition in complex with the xeroderma pigmentosum group C protein. To characterize the dual role of HR23, we have determined the high resolution crystal structure of the mouse peptide
N-glycanase
catalytic core in complex with the xeroderma pigmentosum group C binding domain from
HR23B
. Peptide
N-glycanase
features a large cleft between its catalytic cysteine protease core and zinc binding domain. Opposite the zinc binding domain is the
HR23B
-interacting region, and surprisingly, the complex interface is fundamentally different from the orthologous yeast peptide
N-glycanase
-Rad23 complex. Different regions on both proteins are involved in complex formation, revealing an amazing degree of divergence in the interaction between two highly homologous proteins. Furthermore, the mouse peptide
N-glycanase
-
HR23B
complex mimics the interaction between xeroderma pigmentosum group C and
HR23B
, thereby providing a first structural model of how the two proteins interact within the nucleotide excision repair cascade in higher eukaryotes. The different interaction interfaces of the xeroderma pigmentosum group C binding domains in yeast and mammals suggest a co-evolution of the endoplasmic reticulum-associated degradation and DNA repair pathways.
...
PMID:Structure of the mouse peptide N-glycanase-HR23 complex suggests co-evolution of the endoplasmic reticulum-associated degradation and DNA repair pathways. 1650 Sep 3
