Abstract
African swine fever virus (ASFV) is contagious and can cause highly lethal disease in pigs. ASFV DNA ligase (AsfvLIG) is one of the most error-prone ligases identified to date; it catalyzes DNA joining reaction during DNA repair process of ASFV and plays important roles in mutagenesis of the viral genome. Here, we report four AsfvLIG:DNA complex structures and demonstrate that AsfvLIG has a unique N-terminal domain (NTD) that plays critical roles in substrate binding and catalytic complex assembly. In combination with mutagenesis, in vitro binding and catalytic assays, our study reveals that four unique active site residues (Asn153 and Leu211 of the AD domain; Leu402 and Gln403 of the OB domain) are crucial for the catalytic efficiency of AsfvLIG. These unique structural features can serve as potential targets for small molecule design, which could impair genome repair in ASFV and help combat this virus in the future.
Highlights
African swine fever virus (ASFV) is contagious and can cause highly lethal disease in pigs
ASFV DNA ligase (AsfvLIG) contains one adenylation domain (AD) in the center and one OB-fold domain (OB) at the C-terminus; both AD and OB domains are conserved in homologous proteins (Supplementary Fig. 1), including human DNA ligases (HsLig1-4)[23,24,25], Sus scrofa DNA ligase 1 (SusLIG1), and archaeal ligases[26,27]
We only calculated the simplified apparent rate constants (Kobs) in this study, the full enzymatic characterization leading to both Kcat and Kd values of AsfvLIG has been reported by Lamarche and co-worker previously[13]
Summary
African swine fever virus (ASFV) is contagious and can cause highly lethal disease in pigs. In vitro binding and catalytic assays, our study reveals that four unique active site residues (Asn[153] and Leu[211] of the AD domain; Leu[402] and Gln[403] of the OB domain) are crucial for the catalytic efficiency of AsfvLIG These unique structural features can serve as potential targets for small molecule design, which could impair genome repair in ASFV and help combat this virus in the future. Macrophages are very rich in free oxygen radicals[10,11], which cause constant damages to the virus genome, such as strand breaks and spontaneous depurination/depyrimidation To efficiently overcome these DNA damages, ASFV virus has evolved its own repair system.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
