8YIK

pP1192R-ATPase-domain

Summary for 8YIK

• Entry DOI: 10.2210/pdb8yik/pdb
• Descriptor: DNA topoisomerase 2, ADENOSINE-5'-TRIPHOSPHATE (3 entities in total)
• Functional Keywords: asfv, protein binding, isomerase
• Biological source: African swine fever virus pig/Kenya/KEN-50/1950
• Total number of polymer chains: 1
• Total formula weight: 45465.02

Authors

Sun, J.Q.,Liu, R.L. (deposition date: 2024-02-29, release date: 2024-09-18, Last modification date: 2024-10-30)

Primary citation

Liu, R.,Sun, J.,Li, L.F.,Cheng, Y.,Li, M.,Fu, L.,Li, S.,Peng, G.,Wang, Y.,Liu, S.,Qu, X.,Ran, J.,Li, X.,Pang, E.,Qiu, H.J.,Wang, Y.,Qi, J.,Wang, H.,Gao, G.F.
Structural basis for difunctional mechanism of m-AMSA against African swine fever virus pP1192R.
Nucleic Acids Res., 52:11301-11316, 2024

PubMed Abstract: The African swine fever virus (ASFV) type II topoisomerase (Topo II), pP1192R, is the only known Topo II expressed by mammalian viruses and is essential for ASFV replication in the host cytoplasm. Herein, we report the structures of pP1192R in various enzymatic stages using both X-ray crystallography and single-particle cryo-electron microscopy. Our data structurally define the pP1192R-modulated DNA topology changes. By presenting the A2+-like metal ion at the pre-cleavage site, the pP1192R-DNA-m-AMSA complex structure provides support for the classical two-metal mechanism in Topo II-mediated DNA cleavage and a better explanation for nucleophile formation. The unique inhibitor selectivity of pP1192R and the difunctional mechanism of pP1192R inhibition by m-AMSA highlight the specificity of viral Topo II in the poison binding site. Altogether, this study provides the information applicable to the development of a pP1192R-targeting anti-ASFV strategy.

PubMed: 39166497
DOI: 10.1093/nar/gkae703

Experimental method

X-RAY DIFFRACTION (1.3 Å)