Structural highlights
Function
[NFI_THEMA] Selectively cleaves double-stranded DNA at the second phosphodiester bond 3' to a deoxyinosine leaving behind the intact lesion on the nicked DNA. Acts in DNA repair. In vitro, can also cleave single-stranded substrates with inosine, double-stranded DNA with apurinic sites, or DNA sites with uracil or a mismatched base. When present in molar excess, two protein molecules can bind to the same DNA substrate and effect cleavage of both strands (in vitro).[1]
Publication Abstract from PubMed
Endonuclease V (EndoV) cleaves the second phosphodiester bond 3' to a deaminated adenosine (inosine). Although highly conserved, EndoV homologs change substrate preference from DNA in bacteria to RNA in eukaryotes. We have characterized EndoV from six different species and determined crystal structures of human EndoV and three EndoV homologs from bacteria to mouse in complex with inosine-containing DNA/RNA hybrid or double-stranded RNA (dsRNA). Inosine recognition is conserved, but changes in several connecting loops in eukaryotic EndoV confer recognition of 3 ribonucleotides upstream and 7 or 8 bp of dsRNA downstream of the cleavage site, and bacterial EndoV binds only 2 or 3 nt flanking the scissile phosphate. In addition to the two canonical metal ions in the active site, a third Mn(2+) that coordinates the nucleophilic water appears necessary for product formation. Comparison of EndoV with its homologs RNase H1 and Argonaute reveals the principles by which these enzymes recognize RNA versus DNA.
Evolution of Inosine-Specific Endonuclease V from Bacterial DNase to Eukaryotic RNase.,Wu J, Samara NL, Kuraoka I, Yang W Mol Cell. 2019 Oct 3;76(1):44-56.e3. doi: 10.1016/j.molcel.2019.06.046. Epub 2019, Aug 20. PMID:31444105[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Huang J, Lu J, Barany F, Cao W. Mutational analysis of endonuclease V from Thermotoga maritima. Biochemistry. 2002 Jul 2;41(26):8342-50. PMID:12081482
- ↑ Wu J, Samara NL, Kuraoka I, Yang W. Evolution of Inosine-Specific Endonuclease V from Bacterial DNase to Eukaryotic RNase. Mol Cell. 2019 Oct 3;76(1):44-56.e3. doi: 10.1016/j.molcel.2019.06.046. Epub 2019, Aug 20. PMID:31444105 doi:http://dx.doi.org/10.1016/j.molcel.2019.06.046
