Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.26.9 (ribonuclease)
 6,589 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We previously demonstrated that pneumococcal extracts contain a highly specific inhibitor of human neutrophil elastase (HNE). We now show that the active inhibitor in these extracts is a high-molecular-weight, heat-stable substance that appears to be RNA, since inhibitory activity of pneumococcal extracts is decreased by incubation with ribonuclease but not by incubation with deoxyribonuclease or proteinase K. Moreover, metabolically labeled ([3H]uridine) pneumococcal RNA, isolated by phenol extraction followed by ethanol precipitation, strongly inhibits HNE. Pneumococcal capsular polysaccharide, although polyanionic, is only weakly inhibitory toward HNE and is not a major source of elastase-inhibitory activity in pneumococcal extracts. On the other hand, the capsule of Haemophilus influenzae type b contains polyribosylribitol phosphate. This highly charged polyanion possesses HNE-inhibitory activity, but only under special circumstances to be discussed below. Pneumococci (type I, type II smooth, type II rough) and H. influenzae (type b) all release HNE-inhibitory activity into their culture medium during growth. By contrast, Klebsiella pneumoniae and Staphylococcus aureus release little (if any) stable HNE-inhibitory activity during growth. We propose that some bacterial pneumonias may spare host tissue because polyanions released by the invading microorganisms (e.g. RNA from autolysing pneumococci) inhibit elastase released from inflammatory neutrophils and thereby modulate accompanying tissue proteolysis. Pneumonias caused by microorganisms that do not release stable polyanionic inhibitors of HNE (e.g., Staphylococcus and Klebsiella) may be correspondingly more injurious to the lung.
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PMID:Inhibition of human neutrophil elastase by bacterial polyanions. 244 47

Bacteria have evolved mechanisms that allow them to survive in the face of a variety of stresses including nutrient deprivation, antibiotic challenge and engulfment by predator cells. A switch to dormancy represents one strategy that reduces energy utilization and can render cells resistant to compounds that kill growing bacteria. These persister cells pose a problem during treatment of infections with antibiotics, and dormancy mechanisms may contribute to latent infections. Many bacteria encode toxin-antitoxin (TA) gene pairs that play an important role in dormancy and the formation of persisters. VapBC gene pairs comprise the largest of the Type II TA systems in bacteria and they produce a VapC ribonuclease toxin whose activity is inhibited by the VapB antitoxin. Despite the importance of VapBC TA pairs in dormancy and persister formation, little information exists on the structural features of VapC proteins required for their toxic function in vivo. Studies reported here identified 17 single mutations that disrupt the function of VapC1 from non-typeable H. influenzae in vivo. 3-D modeling suggests that side chains affected by many of these mutations sit near the active site of the toxin protein. Phylogenetic comparisons and secondary mutagenesis indicate that VapC1 toxicity requires an alternative active site motif found in many proteobacteria. Expression of the antitoxin VapB1 counteracts the activity of VapC1 mutants partially defective for toxicity, indicating that the antitoxin binds these mutant proteins in vivo. These findings identify critical chemical features required for the biological function of VapC toxins and PIN-domain proteins.
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PMID:Analysis of non-typeable Haemophilous influenzae VapC1 mutations reveals structural features required for toxicity and flexibility in the active site. 2539 Nov 36