9rif | pdb_00009rif

The histone fold domain heterodimer of oocyst rupture proteins 1 and 2 from Plasmodium berghei

spinqualitylabelsall models 9rif, resolution 3.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9rif is a 12 chain structure with sequence from Plasmodium berghei. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.1Å Ligands: EDO, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A0A509AJ88_PLABA Publication Abstract from PubMed Dimerization between the histone-fold domains (HFD) of two Plasmodium Oocyst Rupture Proteins (ORP1 and ORP2) is essential for oocyst rupture in the Anopheles mosquito vector host, representing a key event in parasite transmission to humans. Notably, ORPs are a rare example of HFD-containing proteins that operate outside the nucleus and that lack DNA-binding functions, typically associated with core histones and transcription factors hosting deviant histones. ORP HFD heterodimerization occurs at the outer capsule of the oocyst, immediately prior to rupture, thus providing a temporal window to administer dimerization blocking molecules. In this context, we present the first detailed structural analysis of the HFD ORP heterodimer, solved by X-ray crystallography at 3.1 A resolution, and analyze the oligomerization interface as a possible druggable target. Targeting the mosquito phase of the parasite lifecycle remains an under-exploited avenue as present antimalarial therapies mainly target the human blood stages of infection. We employed a GAL4-based yeast two-hybrid (Y2H) combinatorial library of cyclic peptides (CPs) to identify six candidates that inhibit dimerization in vitro. Molecular docking simulations confirmed that all six CPs bind at the dimer interface, allowing us to rank them for further in vivo testing of their efficacy in blocking oocyst rupture. Targeting the histone-fold dimerization interface of oocyst rupture proteins from Plasmodium berghei for antimalarial inhibitor discovery.,Ballabio F, Bertaso C, Villa M, Livero O, Del Cont Bernard A, Russo R, Gessmann R, Siden-Kiamos I, Preira CMF, Kumawat A, Gabrieli P, Camilloni C, Curra C, Masiero S, Nardini M, Gourlay LJ FEBS J. 2026 Jan 8. doi: 10.1111/febs.70389. PMID:41506730 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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