6KI3

The crystal structure of AsfvAP:dF commplex

Summary for 6KI3

• Entry DOI: 10.2210/pdb6ki3/pdb
• Descriptor: Probable AP endonuclease, DNA (5'-D(*GP*CP*AP*GP*CP*GP*TP*CP*C)-3'), DNA (5'-D(P*(3DR)P*CP*GP*AP*CP*GP*AP*G)-3'), ... (6 entities in total)
• Functional Keywords: endonucleaseiv, asfv, dna binding protein-dna complex, dna binding protein/dna
• Biological source: African swine fever virus (isolate Tick/South Africa/Pretoriuskop Pr4/1996) (ASFV); More
• Total number of polymer chains: 8
• Total formula weight: 88606.00

Authors

Chen, Y.,Gan, J. (deposition date: 2019-07-17, release date: 2020-05-27, Last modification date: 2024-11-13)

Primary citation

Chen, Y.,Chen, X.,Huang, Q.,Shao, Z.,Gao, Y.,Li, Y.,Yang, C.,Liu, H.,Li, J.,Wang, Q.,Ma, J.,Zhang, Y.Z.,Gu, Y.,Gan, J.
A unique DNA-binding mode of African swine fever virus AP endonuclease.
Cell Discov, 6:13-13, 2020

PubMed Abstract: African swine fever virus (ASFV) is highly contagious and can cause lethal disease in pigs. ASFV is primarily replicated in the cytoplasm of pig macrophages, which is oxidative and caused constant damage to ASFV genome. ASFV AP endonuclease (AP) catalyzes DNA cleavage reaction at the abasic site and is a key enzyme of ASFV base excision repair (BER) system. Although it plays an essential role in ASFV survival in host cells, the basis underlying substrate binding and cleavage by AP remains unclear. Here, we reported the structural and functional studies of AP, showing that AP adopts a novel DNA-binding mode distinct from other APs. AP possesses many unique structural features, including one narrower nucleotide-binding pocket at the active site, the C16-C20 disulfide bond-containing region, and histidine-rich loop. As indicated by our mutagenesis, in vitro binding and cleavage assays, these features are important for AP to suit the acidic and oxidative environment. Owing to their functional importance, these unique features could serve as targets for designing small molecule inhibitors that could disrupt the repair process of ASFV genome and help fight against this deadly virus in the future.

PubMed: 32194979
DOI: 10.1038/s41421-020-0146-2

Experimental method

X-RAY DIFFRACTION (2.354 Å)