8RXA
ACDC domain of AP2-O5 from Plasmodium falciparum
Summary for 8RXA
| Entry DOI | 10.2210/pdb8rxa/pdb |
| Descriptor | AP2 domain transcription factor AP2-O5, putative (2 entities in total) |
| Functional Keywords | ap2-coincident domain mainly at the c-terminus, orthogonal four helix bundle, transcription |
| Biological source | Plasmodium falciparum 3D7 |
| Total number of polymer chains | 2 |
| Total formula weight | 23529.31 |
| Authors | Nessler, S.,Le Berre, M.,Gallay Li de la Sierra, I. (deposition date: 2024-02-06, release date: 2024-03-06) |
| Primary citation | Le Berre, M.,Tubiana, T.,Reutersward Waldner, P.,Lazar, N.,Li de la Sierra, I.,Santos, J.M.,Llinas, M.,Nessler, S. Structural characterization of the ACDC domain from ApiAP2 proteins of the malaria parasite. Biorxiv, 2024 Cited by PubMed Abstract: The Apicomplexan AP2 (ApiAP2) proteins are the best characterized family of DNA-binding proteins in the malaria parasite. Apart from the AP2 DNA-binding domain, there is little sequence similarity between ApiAP2 proteins and no other functional domains have been extensively characterized. One protein domain, which is present in a subset of the ApiAP2 proteins, is the conserved AP2-coincident domain mostly at the C-terminus (ACDC domain). Here we solved for the first time the crystal structure of the ACDC domain from two distinct ApiAP2 proteins and one orthologue from , revealing a non-canonical four-helix bundle. Despite little sequence conservation between the ACDC domains from the two proteins, the structures are remarkably similar and do not resemble that of any other known protein domains. Due to their unique protein architecture and lack of homologues in the human genome, we performed docking calculations against a library of known antimalarial compounds and we identified a small molecule that can potentially bind to any Apicomplexan ACDC domain within a pocket highly conserved amongst ApiAP2 proteins. Inhibitors based on this compound would disrupt the function of the ACDC domain and thus of the ApiAP2 proteins containing it, providing a new therapeutic window for targeting the malaria parasite and other Apicomplexans. PubMed: 38370614DOI: 10.1101/2024.02.09.579679 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.751 Å) |
Structure validation
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