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Structure paper

TitleStructural basis for difunctional mechanism of m-AMSA against African swine fever virus pP1192R.
Journal, issue, pagesNucleic Acids Res, Year 2024
Publish dateAug 21, 2024
AuthorsRuili Liu / Junqing Sun / Lian-Feng Li / Yingxian Cheng / Meilin Li / Lifeng Fu / Su Li / Guorui Peng / Yanjin Wang / Sheng Liu / Xiao Qu / Jiaqi Ran / Xiaomei Li / Erqi Pang / Hua-Ji Qiu / Yanli Wang / Jianxun Qi / Han Wang / George Fu Gao /
PubMed AbstractThe 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. ...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.
External linksNucleic Acids Res / PubMed:39166497
MethodsEM (single particle) / X-ray diffraction
Resolution1.3 - 3.23 Å
Structure data

EMDB-39077: pP1192R-DNA-m-AMSA complex Overall-2
Method: EM (single particle) / Resolution: 3.17 Å

EMDB-39078: pP1192R-DNA-m-AMSA complex Overall-1
Method: EM (single particle) / Resolution: 3.23 Å

EMDB-39245, PDB-8yge:
pP1192R-DNA-m-AMSA complex DNA binding/cleavage domain
Method: EM (single particle) / Resolution: 2.76 Å

EMDB-39249, PDB-8ygg:
pP1192R-apo Closed state
Method: EM (single particle) / Resolution: 2.98 Å

EMDB-39250, PDB-8ygh:
pP1192R-apo open state
Method: EM (single particle) / Resolution: 2.77 Å

PDB-8yik:
pP1192R-ATPase-domain
Method: X-RAY DIFFRACTION / Resolution: 1.3 Å

Chemicals

ChemComp-MG:
Unknown entry

ChemComp-ASW:
N-[4-(acridin-9-ylamino)-3-methoxyphenyl]methanesulfonamide / antineoplastic*YM

ChemComp-ATP:
ADENOSINE-5'-TRIPHOSPHATE / ATP, energy-carrying molecule*YM

ChemComp-HOH:
WATER

Source
  • African swine fever virus
  • african swine fever virus pig/kenya/ken-50/1950
KeywordsISOMERASE/DNA / ASFV / PROTEIN BINDING / ISOMERASE-DNA complex / ISOMERASE

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