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European Journal of Medicinal Chemistry Dec 2014Deoxyribonucleases (DNases) are a class of enzymes able to catalyze DNA hydrolysis. DNases play important roles in cell function, while DNase inhibitors control or... (Review)
Review
Deoxyribonucleases (DNases) are a class of enzymes able to catalyze DNA hydrolysis. DNases play important roles in cell function, while DNase inhibitors control or modify their activities. This review focuses on DNase inhibitors. Some DNase inhibitors have been isolated from various natural sources, such as humans, animals (beef, calf, rabbit and rat), plants (Nicotiana tabacum), and microorganisms (some Streptomyces and Adenovirus species, Micromonospora echinospora and Escherichia coli), while others have been obtained by chemical synthesis. They differ in chemical structure (various proteins, nucleotides, anthracycline and aminoglycoside antibiotics, synthetic organic and inorganic compounds) and mechanism of action (forming complexes with DNases or DNA). Some of the inhibitors are specific toward only one type of DNase, while others are active towards two or more. Physico-chemical properties of DNase inhibitors are calculated using the Molinspiration tool and most of them meet all criteria for good solubility and permeability. DNase inhibitors may be used as pharmaceuticals for preventing, monitoring and treating various diseases.
Topics: Animals; Deoxyribonucleases; Enzyme Inhibitors; Humans; Molecular Structure; Structure-Activity Relationship
PubMed: 25042005
DOI: 10.1016/j.ejmech.2014.07.040 -
Trends in Genetics : TIG Aug 2021Cell-free DNA (cfDNA) is a widely used noninvasive biomarker for diagnosis and prognosis of multiple disease states. Emerging evidence suggests that cfDNA might not just... (Review)
Review
Cell-free DNA (cfDNA) is a widely used noninvasive biomarker for diagnosis and prognosis of multiple disease states. Emerging evidence suggests that cfDNA might not just be passive waste products of cell death but could have a physiological and pathological function in inflammation and autoimmunity. The balance of cfDNA generation and clearance may thus be vital in health and disease. In particular, plasma nuclease activity has been linked to multiple pathologies including cancer and systemic lupus erythematosus (SLE) and associated with profound changes in the nonrandom fragmentation of cfDNA. Lastly, in this review, we explore the effects of DNA fragmentation factor B (DFFB), DNASE1L3, and DNASE1 on cfDNA levels and their fragmentomic profiles, and what these recent insights reveal about the biology of cfDNA.
Topics: Autoimmunity; Cell-Free Nucleic Acids; DNA Fragmentation; Deoxyribonuclease I; Deoxyribonucleases; Endodeoxyribonucleases; Humans; Inflammation; Poly-ADP-Ribose Binding Proteins
PubMed: 34006390
DOI: 10.1016/j.tig.2021.04.005 -
Gene Jun 2022Deoxyribonuclease II (DNase II) has been found to regulate inflammation, autoimmunity and apoptosis in vertebrates and invertebrates. The strong capacity of degrading...
Deoxyribonuclease II (DNase II) has been found to regulate inflammation, autoimmunity and apoptosis in vertebrates and invertebrates. The strong capacity of degrading DNA makes DNase II play an important role in the immune process. Planarian has become one of the model references due to its strong immune system, the environment they live makes planarians face the threat of microorganisms and injury, the strong immune system can protect planarians from the threat of bacterial and infection. In this study, we found that there was DNase in the lysis buffer of planarians, then we acquired the sequence of DjDN2s (Dugesia japonica DNase2s) and confirmed the DjDN2s were conserved DNase IIs. The predicted structure showed the active sites and binding patterns of DjDN2s. Whole-mount in situ hybridization results showed DjDN2s mainly expressed in immune organs. Quantitative real-time PCR revealed that the expression of DjDN2s upregulated in varying degrees when got hurt and challenged with bacteria, and the knockdown of DjDN2s led to the slower repair of wound. The recombinant phages which take DjDN2 also had the ability to degrade DNA and clear young biofilm of Gram-negative bacteria. Collectively, DNase II of planarian might play a role in the antimicrobial response and wound-induced response.
Topics: Animals; Deoxyribonucleases; Endodeoxyribonucleases; Planarians
PubMed: 35358655
DOI: 10.1016/j.gene.2022.146464 -
Molecular and Cellular Biochemistry Jan 1981This article will review recent progress on the purification of DNase I (E.C.3.1.4.5) from various sources and the characterization of multiple forms of the enzyme. The... (Review)
Review
This article will review recent progress on the purification of DNase I (E.C.3.1.4.5) from various sources and the characterization of multiple forms of the enzyme. The chemical basis of the multiple forms in bovine pancreas will be discussed in detail, while for other DNases, including those in ovine pancreas, bovine, mouse and rat parotid, and malt, only the evidence for multiplicity will be discussed in detail, while for other DNases, including those in ovine pancreas, bovine, mouse and rat parotid, and malt, only the evidence for multiplicity will be presented.
Topics: Amino Acid Sequence; Animals; Cattle; Chemical Phenomena; Chemistry; Deoxyribonuclease I; Deoxyribonucleases; Endonucleases; Hordeum; Macromolecular Substances; Mice; Molecular Weight; Organ Specificity; Pancreas; Parotid Gland; Rats; Sheep; Sialic Acids; Species Specificity
PubMed: 6262624
DOI: 10.1007/BF02354847 -
Applied Microbiology Jul 1970Use of the agar plate test for the enzyme deoxyribonucleate 3'-nucleotidohydrolase (deoxyribonuclease) can result in frequent misdiagnosis of Staphylococcus epidermidis...
Use of the agar plate test for the enzyme deoxyribonucleate 3'-nucleotidohydrolase (deoxyribonuclease) can result in frequent misdiagnosis of Staphylococcus epidermidis as S. aureus.
Topics: Agar; Bacteriological Techniques; Bacteriophage Typing; Coagulase; Deoxyribonucleases; Staphylococcus
PubMed: 4917463
DOI: 10.1128/am.20.1.54-57.1970 -
Frontiers in Immunology 2023Neutrophil Extracellular Traps (NETs) are key mediators of immunothrombotic mechanisms and defective clearance of NETs from the circulation underlies an array of...
BACKGROUND
Neutrophil Extracellular Traps (NETs) are key mediators of immunothrombotic mechanisms and defective clearance of NETs from the circulation underlies an array of thrombotic, inflammatory, infectious, and autoimmune diseases. Efficient NET degradation depends on the combined activity of two distinct DNases, DNase1 and DNase1-like 3 (DNase1L3) that preferentially digest double-stranded DNA (dsDNA) and chromatin, respectively.
METHODS
Here, we engineered a dual-active DNase with combined DNase1 and DNase1L3 activities and characterized the enzyme for its NET degrading potential in vitro. Furthermore, we produced a mouse model with transgenic expression of the dual-active DNase and analyzed body fluids of these animals for DNase1 and DNase 1L3 activities. We systematically substituted 20 amino acid stretches in DNase1 that were not conserved among DNase1 and DNase1L3 with homologous DNase1L3 sequences.
RESULTS
We found that the ability of DNase1L3 to degrade chromatin is embedded into three discrete areas of the enzyme's core body, not the C-terminal domain as suggested by the state-of-the-art. Further, combined transfer of the aforementioned areas of DNase1L3 to DNase1 generated a dual-active DNase1 enzyme with additional chromatin degrading activity. The dual-active DNase1 mutant was superior to native DNase1 and DNase1L3 in degrading dsDNA and chromatin, respectively. Transgenic expression of the dual-active DNase1 mutant in hepatocytes of mice lacking endogenous DNases revealed that the engineered enzyme was stable in the circulation, released into serum and filtered to the bile but not into the urine.
CONCLUSION
Therefore, the dual-active DNase1 mutant is a promising tool for neutralization of DNA and NETs with potential therapeutic applications for interference with thromboinflammatory disease states.
Topics: Mice; Animals; Endodeoxyribonucleases; Extracellular Traps; Deoxyribonuclease I; Chromatin; DNA; Deoxyribonucleases
PubMed: 37287977
DOI: 10.3389/fimmu.2023.1181761 -
The Journal of Antibiotics Feb 1982
Topics: Deoxyribonucleases; Micromonospora
PubMed: 7076569
DOI: 10.7164/antibiotics.35.248 -
The Journal of Biological Chemistry Apr 1974
Topics: Amino Acid Sequence; Amino Acids; Animals; Calcium; Carbohydrates; Cattle; Chromatography, DEAE-Cellulose; Chromatography, Ion Exchange; Chymotrypsin; Deoxyribonucleases; Drug Stability; Glycoproteins; Neuraminic Acids; Osmolar Concentration; Pancreas; Peptide Fragments; Peptide Hydrolases; Trypsin
PubMed: 4856650
DOI: No ID Found -
Archives of Andrology May 1983Deoxyribonuclease (DNase) activity was examined in the whole and two split fractions of human seminal fluid from normospermic, oligozoospermic, and azoospermic origins...
Deoxyribonuclease (DNase) activity was examined in the whole and two split fractions of human seminal fluid from normospermic, oligozoospermic, and azoospermic origins as well as in sonicates of isolated sperm after freezing and thawing of samples and at various pH values of substrates. The method consisted in the measurement of digested areas in plates containing herring sperm deoxyribonucleic acid (DNA). No correlation was found between DNase activity (875 +/- 22 (SE) ng/ml) and seminal fluid quality. The enzyme activity was significantly lower in the second split portion (764 +/- 43 ng/ml) as compared to the first (971 +/- 41 ng/ml). Sonicates of washed sperm were inactive. It is suggested that DNase activity derives from the epididymis and possibly from the vas deferens where it participates in the decomposition of DNA from dead cells.
Topics: Deoxyribonucleases; Humans; Hydrogen-Ion Concentration; Male; Semen; Sperm Count
PubMed: 6860038
DOI: 10.3109/01485018308987559 -
The Journal of Applied Bacteriology Aug 1991Myxococcus coralloides D produced cell-bound deoxyribonucleases (DNases) during the exponential phase of growth in liquid medium. DNase activity was much higher than...
Myxococcus coralloides D produced cell-bound deoxyribonucleases (DNases) during the exponential phase of growth in liquid medium. DNase activity was much higher than that detected in other myxobacterial strains and was fractionated into three different peaks by filtration through Sephadex G-200. The DNases were named G, M and P. The optimum temperatures were 37 degrees C, 33 degrees C and 25 degrees C respectively, although high activities were recorded over the temperature range 20-45 degrees C. The pH range of high activity was between 6.0 and 9.0, with an optimum for each DNase at 8.0. DNases M and P were strongly inhibited by low concentrations of NaCl, but activity of DNase G was less affected by NaCl. The three activities required divalent metal ions as cofactors (especially Mg2+ and Mn2+); however, other metal ions (Fe2+, Ni2+, Zn2+) were inhibitors. The molecular weights were estimated by gel filtration chromatography and SDS-PAGE as 44 kDa (DNase G), 49 kDa (DNase M) and 39 kDa (DNase P).
Topics: Chromatography, Gel; Deoxyribonucleases; Electrophoresis, Polyacrylamide Gel; Hydrogen-Ion Concentration; Magnesium; Manganese; Molecular Weight; Myxococcus; Sodium Chloride; Temperature
PubMed: 1917725
DOI: 10.1111/j.1365-2672.1991.tb02974.x