8RWU

ACDC domain of the AP2-I transcription factor from Plasmodium vivax

Summary for 8RWU

• Entry DOI: 10.2210/pdb8rwu/pdb
• Descriptor: AP2 domain transcription factor AP2-I, putative (1 entity in total)
• Functional Keywords: ap2-coincident domain mainly at the c-terminus, orthogonal four helix bundle, transcription, unknown function
• Biological source: Plasmodium vivax (malaria parasite P. vivax)
• Total number of polymer chains: 2
• Total formula weight: 46649.62

Authors

Nessler, S.,Le Berre, M.,Gallay Li de la Sierra, I. (deposition date: 2024-02-05, release date: 2024-03-06, Last modification date: 2025-01-29)

Primary citation

Le Berre, M.,Tubiana, T.,Reutersward Waldner, P.,Lazar, N.,Li de la Sierra-Gallay, I.,Santos, J.M.,Llinas, M.,Nessler, S.
Structural characterization of the ACDC domain from ApiAP2 proteins, a potential molecular target against apicomplexan parasites.
Acta Crystallogr D Struct Biol, 81:38-48, 2025

PubMed Abstract: The apicomplexan AP2 (ApiAP2) proteins are the best characterized family of DNA-binding proteins in Plasmodium spp. malaria parasites. Apart from the AP2 DNA-binding domain, there is little sequence similarity between ApiAP2 proteins. However, a conserved AP2-coincident domain mostly at the C-terminus (ACDC domain) is observed in a subset of the ApiAP2 proteins. The structure and function of this domain remain unknown. We report two crystal structures of ACDC domains derived from distinct Plasmodium ApiAP2 proteins, revealing a conserved, unique, noncanonical, four-helix bundle architecture. We used these structures to perform in silico docking calculations against a library of known antimalarial compounds and identified potential small-molecule ligands that bind in a highly conserved hydrophobic pocket that is present in all apicomplexan ACDC domains. These ligands provide a new molecular basis for the future design of ACDC inhibitors.

PubMed: 39820027
DOI: 10.1107/S2059798324012518

Experimental method

X-RAY DIFFRACTION (3.15 Å)