Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.27.5 (RNase)
 17,967 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The disulfide-bond isomerase DsbC plays a crucial role in the folding of bacterial proteins in the periplasmic space. DsbC has a V-shaped dimeric structure with two domains, and Cys98 in the C-terminal domain attacks inappropriate disulfide bonds in substrate proteins due to its high nucleophilic activity. In this article, we present the crystal structure of DsbC from Salmonella enterica serovar Typhimurium. We evaluated the conserved residues Asp95 and Arg125, which are located close to Cys98. The mutation of Asp95 or Arg125 abolished the disulfide isomerase activity of DsbC in an in vitro assay using a protein substrate, and the R125A mutation significantly reduced the chaperone activity for the substrate RNase I in vivo. Furthermore, a comparative analysis suggested that the conformation of Arg125 varies depending on the packing or protein-protein interactions. Based on these findings, we suggest that Asp95 and Arg125 modulate the pKa of Cys98 during catalysis.
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PMID:Crystal structure of the periplasmic disulfide-bond isomerase DsbC from Salmonella enterica serovar Typhimurium and the mechanistic implications. 2372 83

In the endoplasmic reticulum (ER), ER oxidoreductin 1 (ERO1) catalyzes intramolecular disulfide-bond formation within its substrates in coordination with protein-disulfide isomerase (PDI) and related enzymes. However, the molecular mechanisms that regulate the ERO1-PDI system in plants are unknown. Reduction of the regulatory disulfide bonds of the ERO1 from soybean, GmERO1a, is catalyzed by enzymes in five classes of PDI family proteins. Here, using recombinant proteins, vacuum-ultraviolet circular dichroism spectroscopy, biochemical and protein refolding assays, and quantitative immunoblotting, we found that GmERO1a activity is regulated by reduction of intramolecular disulfide bonds involving Cys-121 and Cys-146, which are located in a disordered region, similarly to their locations in human ERO1. Moreover, a GmERO1a variant in which Cys-121 and Cys-146 were replaced with Ala residues exhibited hyperactive oxidation. Soybean PDI family proteins differed in their ability to regulate GmERO1a. Unlike yeast and human ERO1s, for which PDI is the preferred substrate, GmERO1a directly transferred disulfide bonds to the specific active center of members of five classes of PDI family proteins. Of these proteins, GmPDIS-1, GmPDIS-2, GmPDIM, and GmPDIL7 (which are group II PDI family proteins) failed to catalyze effective oxidative folding of substrate RNase A when there was an unregulated supply of disulfide bonds from the C121A/C146A hyperactive mutant GmERO1a, because of its low disulfide-bond isomerization activity. We conclude that regulation of plant ERO1 activity is particularly important for effective oxidative protein folding by group II PDI family proteins.
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PMID:Regulation of plant ER oxidoreductin 1 (ERO1) activity for efficient oxidative protein folding. 3168 60


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