Structure of acid deoxyribonuclease

Abstract

Deoxyribonuclease II (DNase II) is also known as acid deoxyribonuclease because it has optimal activity at the low pH environment of lysosomes where it is typically found in higher eukaryotes. Interestingly, DNase II has also been identified in a few genera of bacteria and is believed to have arisen via horizontal transfer. Here, we demonstrate that recombinant Burkholderia thailandensis DNase II is highly active at low pH in the absence of divalent metal ions, similar to eukaryotic DNase II. The crystal structure of B. thailandensis DNase II shows a dimeric quaternary structure which appears capable of binding double-stranded DNA. Each monomer of B. thailandensis DNase II exhibits a similar overall fold as phospholipase D (PLD), phosphatidylserine synthase (PSS) and tyrosyl-DNA phosphodiesterase (TDP), and conserved catalytic residues imply a similar mechanism. The structural and biochemical data presented here provide insights into the atomic structure and catalytic mechanism of DNase II.

Pyronaridine exerts potent cytotoxicity on human breast and hematological cancer cells through induction of apoptosis

“…In these DNA binding assays, the experimental compound-DNA complexes migrate more slowly than the free DNA (uncomplexed DNA control), which results in DNA having a heavier molecular weight. Additionally, when incubating a chemical compound with plasmid DNA, it is possible to detect if there are any deleterious effects resulting in DNA degradation or fragmentation [ 36 ]. Our results indicate that PND interacts directly with DNA since it causes significant DNA retardation in agarose gels, in a concentration-depended manner but did not cause DNA degradation [ 14 ].…”

Nematodes Degrade Extracellular Antibiotic Resistance Genes by Secreting DNase II Encoded by the nuc-1 Gene

“…28,53−55 EDTA is a common metal ion chelator and inhibits enzymes requiring divalent metal ions, including DNase I. 28,56 The addition of different EDTA concentrations appeared not to inhibit plasmid degradation by ESP (Figure 2E and Figure S3E). In contrast, the degradation by purchased DNase I was suppressed (Figure 2F).…”

“…26,27 DNase II in lysosomes has been predicted to prevent horizontal gene transfer of foreign DNA into the host genome by generating of 3′-phosphate and 5′-hydroxyl DNA fragments with nonligatable ends. 28,29 Nonparasitic nematodes, particularly bacterivorous taxa, fill an ecological niche that requires them to ingest DNA-based bacterial aggregation or biofilms to obtain food. 30,31 It is therefore possible that they preserve the same skill of DNA degradation as parasitic worms.…”

A virus changed my life

“…My lab purified the nuclease that I had discovered as a graduate student, and we eventually obtained several peptide sequences that led to the cloning of the nuclease gene and resulted in my first patent ( Lyon et al , 1996, 2000 ; Lyon and Aguilera, 1997 ). We subsequently cloned the nuclease gene from several organisms and obtained active recombinant protein, which allowed us to determine its protein structure in 2017 ( Evans et al , 2002 ; Evans and Aguilera, 2003 ; Varela-Ramirez et al , 2017 ). Interestingly, knockdown of this enzyme in Drosophila resulted in impaired immune function, which led to the discovery of another nuclease, which we named stress-induced DNase (SID) since it is activated by infection and chemical stress ( Seong et al , 2006 , 2014).…”