Modeling of Escherichia coli Endonuclease V structure in complex with DNA

Endonuclease V (EndoV) is a metal-dependent DNA repair enzyme involved in removal of deaminated bases (e.g., deoxyuridine, deoxyinosine, and deoxyxanthosine), with pairing specificities different from the original bases. Homologs of EndoV are present in all major phyla from bacteria to humans and their function is quite well analyzed. EndoV has been combined with DNA ligase to develop an enzymatic method for mutation scanning and has been engineered to obtain variants with different substrate specificities that serve as improved tools in mutation recognition and cancer mutation scanning. However, little is known about the structure and mechanism of substrate DNA binding by EndoV. Here, we present the results of a bioinformatic analysis and a structural model of EndoV from Escherichia coli in complex with DNA. The structure was obtained by a combination of fold-recognition, comparative modeling, de novo modeling and docking methods. The modeled structure provides a convenient tool to study protein sequence-structure-function relationships in EndoV and to engineer its further variants.