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:3.1.27.1 (
RNase
)
16,360
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Recent evidence suggests antimicrobial peptides protect the urinary tract from infection. Ribonuclease 7 (RNase 7), a member of the RNase A superfamily, is a potent epithelial-derived protein that maintains human urinary tract sterility. RNase 7 expression is restricted to primates, limiting evaluation of its antimicrobial activity in vivo. Here we identified
ribonuclease 6
(
RNase
6) as the RNase A superfamily member present in humans and mice that is most conserved at the amino acid level relative to RNase 7. Like RNase 7, recombinant human and murine
RNase
6 has potent antimicrobial activity against uropathogens. Quantitative real-time PCR and immunoblot analysis indicate that
RNase
6 mRNA and protein are upregulated in the human and murine urinary tract during infection. Immunostaining located
RNase
6 to resident and infiltrating monocytes, macrophages, and neutrophils. Uropathogenic E. coli induces
RNase
6 peptide expression in human CD14(+) monocytes and murine bone marrow-derived macrophages. Thus,
RNase
6 is an inducible, myeloid-derived protein with markedly different expression from the epithelial-derived RNase 7 but with equally potent antimicrobial activity. Our studies suggest
RNase
6 serves as an evolutionarily conserved antimicrobial peptide that participates in the maintenance of urinary tract sterility.
...
PMID:Ribonucleases 6 and 7 have antimicrobial function in the human and murine urinary tract. 2507 72
Ribonuclease 6
(
RNase
6) is one of eight catalytically active human pancreatic-type RNases that belong to a superfamily of rapidly evolving enzymes. Like some of its human homologues,
RNase
6 exhibits host defense properties such as antiviral and antibacterial activities. Recently solved crystal structures of this enzyme in its nucleotide-free form show the conservation of the prototypical kidney-shaped fold preserved among vertebrate RNases, in addition to revealing the presence of a unique secondary active site. In this study, we determine the structural and conformational properties experienced by
RNase
6 upon binding to substrate and product analogues. We present the first crystal structures of
RNase
6 bound to a nucleotide ligand (adenosine 5'-monophosphate), in addition to
RNase
6 bound to phosphate ions. While the enzyme preserves B
2
subsite ligand preferences, our results show a lack of typical B
2
subsite interactions normally observed in homologous ligand-bound RNases. A comparison of the dynamical properties of
RNase
6 in its apo-, substrate-, and product-bound states highlight the unique dynamical properties experienced on time scales ranging from nano- to milliseconds. Overall, our results confirm the specific evolutionary adaptation of
RNase
6 relative to its unique catalytic and biological activities.
...
PMID:Insights into Structural and Dynamical Changes Experienced by Human RNase 6 upon Ligand Binding. 3190 2
