title: Antimalarial drug quinacrine binds to C-terminal helix of cellular prion protein.
abstract: Using NMR spectroscopy we show that the cellular prion protein constitutes a target for binding of various acridine and phenothiazine derivatives. We unambiguously map the quinacrine binding site of recombinant human prion protein to residues Tyr225, Tyr226, and Gln227 of helix alpha3, which is located near the "protein X" epitope. The millimolar dissociation constant of the complex suggests that in vivo inhibition of prion propagation occurs after 10000-fold concentration of quinacrine within endolysosomes.
authors.affiliation: Institut für Molekularbiologie und Biophysik, Eidgenössische Technische Hochschule Zürich, CH-8093 Zürich, Switzerland.
authors.forename: Martin
authors.initials: M
authors.lastname: Vogtherr
authors.forename: Susanne
authors.initials: S
authors.lastname: Grimme
authors.forename: Bettina
authors.initials: B
authors.lastname: Elshorst
authors.forename: Doris M
authors.initials: DM
authors.lastname: Jacobs
authors.forename: Klaus
authors.initials: K
authors.lastname: Fiebig
authors.forename: Christian
authors.initials: C
authors.lastname: Griesinger
authors.forename: Ralph
authors.initials: R
authors.lastname: Zahn
mesh_terms: D000962:Antimalarials / Q000737:chemistry*; D001665:Binding Sites; D002738:Chloroquine / Q000737:chemistry; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D010446:Peptide Fragments / Q000737:chemistry; D010640:Phenothiazines / Q000737:chemistry; D011328:Prions / Q000737:chemistry*; D017433:Protein Structure, Secondary; D011796:Quinacrine / Q000737:chemistry*; D011994:Recombinant Proteins / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D000962:Antimalarials; D010446:Peptide Fragments; D010640:Phenothiazines; D011328:Prions; D011994:Recombinant Proteins; D002738:Chloroquine; D011796:Quinacrine