Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.27.4 (ribonuclease)
 6,621 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Using sensitive sequence profile searches and contextual information gleaned from domain architectures and predicted operons we identify a novel family of protein domains with predicted ribonuclease activity. These domains are found in the eukaryotic proteins typified by the Nedd4-binding protein 1 and the bacterial YacP-like proteins (Nedd4-BP1, YacP nucleases; NYN domains). We show that the NYN domain shares a common protein fold with two other previously characterized groups of nucleases, namely the PIN (PilT N-terminal) and FLAP/5' --> 3' exonuclease superfamilies. We also show that all these proteins share a common set of 4 acidic conserved residues that are predicted to constitute their active site. Based on the conservation of the acidic residues and structural elements we suggest that PIN and NYN domains are likely to bind only a single metal ion, unlike the FLAP/5' --> 3' exonuclease superfamily, which binds two metal ions. We also present evidence that the other conserved residues shared by all these three domains are likely to play critical roles in sensing the substrate and positioning the catalytic residues in the right conformation. Based on conserved gene neighborhoods we infer that the bacterial members are likely to be components of the processome/degradsome that process tRNAs or ribosomal RNAs. Eukaryotic versions appear to have undergone extensive functional diversification as suggested by the several distinctive multi-domain architectures showing fusions with various other RNA-binding domains like CCCH, PPR and KH domains. Interestingly, the eukaryotic NYN domains also show multiple fusions to the UBA domain, an ubiquitin-binding adaptor domain. This observation, together with the monoubiquitination of Nedd4-BP1 by the ubiquitin ligase Nedd4 suggests that the NYN domain proteins of eukaryotes are regulated by monoubiquitination. Given the localization of Nedd4-BP1 to punctuate nuclear bodies, it is likely that they are parts of nuclear RNA-processing complexes that are dependent on monoubiquitination for their assembly.
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PMID:The NYN domains: novel predicted RNAses with a PIN domain-like fold. 1711 34

Fbs1 is a cytosolic lectin putatively operating as a chaperone as well as a substrate-recognition subunit of the SCF(Fbs1) ubiquitin ligase complex. To provide structural and functional basis of preferential binding of Fbs1 to unfolded glycoproteins, we herein characterize the interaction of Fbs1 with a heptapeptide carrying Man3GlcNAc2 by nuclear magnetic resonance (NMR) spectroscopy and other biochemical methods. Inspection of the NMR data obtained by use of the isotopically labeled glycopeptide indicated that Fbs1 interacts with sugar-peptide junctions, which are shielded in native glycoprotein, in many cases, but become accessible to Fbs1 in unfolded glycoproteins. Furthermore, Fbs1 was shown to inhibit deglycosylation of denatured ribonuclease B by a cytosolic peptide:N-glycanase (PNGase). On the basis of these data, we suggest that Fbs1 captures malfolded glycoproteins, protecting them from the attack of PNGase, during the chaperoning or ubiquitinating operation in the cytosol.
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PMID:Fbs1 protects the malfolded glycoproteins from the attack of peptide:N-glycanase. 1772 Jan 38