title: Computational studies of transition metal selectivity of octapeptide repeat region of prion protein (PrP).
abstract: We have presented a detailed theoretical (density functional theory and ONIOM) study on the structure and M-PrP (prion protein) interaction on various prion models, M(PrP) systems (where PrP = HGG, HGGGW x 3H(2)O, and PrP(61-84), and M = Zn, Cu, Ni, Co, Fe, Mn). It was shown that the geometry of the complex [Mn(HGGGW)(H(2)O)] x 2H(2)O is quite different for M = Mn(III) and Mn(II), and partial unfolding occurs only for the M = Mn(III). In [Zn{PrP(61-84)}], Zn(II) forms a bond with carbonyl oxygen of the Pro(84) residue in the axial position. The coordination of transition metal ions to PrP(61-84) induces the significant geometrical changes in the PrP(61-68) and Prp(69-76) octapeptide repeat regions. The Trp(65) and Trp(73) residues come closer to each other. The glutamines Gln(67) and Gln(75) also come closer to one another and result in the formation of a hydrogen bond between the carbonyl carbon of Gln(67) and one of the NH(2) hydrogens of Gln(75). A specific aggregatory effect is found for Co(II) and Mn(II). The relative binding ability of the metal ions increases in the order Zn(II) < Mn(II) < Cu(II) < Fe(II) < Co(II) < Ni(II). The PrP is most distorted upon binding to Co(II) and least distorted upon binding to Zn(II).
authors.affiliation: School of Chemical Sciences, Devi Ahilya University Indore, Indore 452001, India. kkpandey.schem@dauniv.ac.in
authors.forename: Krishna K
authors.initials: KK
authors.lastname: Pandey
authors.forename: James P
authors.initials: JP
authors.lastname: Snyder
authors.forename: Dennis C
authors.initials: DC
authors.lastname: Liotta
authors.forename: Djamaladdin G
authors.initials: DG
authors.lastname: Musaev
mesh_terms: D000818:Animals; D001665:Binding Sites; D006801:Humans; D008670:Metals / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D008968:Molecular Conformation; D011328:Prions / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D020449:Repetitive Sequences, Amino Acid; D028561:Transition Elements / Q000737:chemistry / Q000378:metabolism*
chemical_list: D008670:Metals; D011328:Prions; D028561:Transition Elements