title: Metal-dependent hydrolysis of myelin basic protein by IgGs from the sera of patients with multiple sclerosis.
abstract: Homogeneous IgG fractions were obtained by chromatography of the sera of patients with multiple sclerosis (MS) on Protein G-Sepharose under conditions that remove non-specifically bound proteins. These IgGs contained several chelated metals, the relative amount of which decreases in the order: Fe>or=Ca>Cu>or=Zn>or=Mg>or=Mn>or=Pb>or=Co>or=Ni. In contrast to homogeneous IgGs of healthy individuals, Abs of MS patients effectively hydrolyzed human myelin basic protein (MBP). A minor metal-dependent fraction was obtained by chromatography of highly purified IgGs from MS patient on Chelex-100. This IgG fraction did not hydrolyze human MBP in the absence of Me(2+) ions but was activated after addition of Me(2+) ions: Mg(2+)>Mn(2+)>Cu(2+)>Ca(2+). Proteolytic activities of IgGs from other MS patients were also activated by other metal ions (Ni(2+), Fe(2+), Co(2+), Zn(2+), Pb(2+), and Co(2+)) and especially Ni(2+). Ni(2+)-activated IgGs were separated into distinct MBP-hydrolyzing fractions by chromatography on HiTraptrade mark Chelating Sepharose charged with Ni(2+). Detection of Mg(2+)-dependent proteolytic activity in the SDS-PAGE area corresponding only to IgG provided direct evidence that IgG from sera of MS patients possesses metal-dependent human MBP-hydrolyzing activity. Observed properties of MS abzymes distinguish them from other known mammalian metalloproteases and demonstrate their pronounced catalytic diversity. Metal-dependent IgGs from MS patients represent the first example of abzymes with metal-dependent proteolytic activity.
authors.affiliation: Institute of Chemical Biology and Fundamental Medicine, Siberian Division of Russian Academy of Sciences, Novosibirsk, Russia.
authors.forename: Dar'ya I
authors.initials: DI
authors.lastname: Polosukhina
authors.forename: Tat'yana G
authors.initials: TG
authors.lastname: Kanyshkova
authors.forename: Boris M
authors.initials: BM
authors.lastname: Doronin
authors.forename: Olga B
authors.initials: OB
authors.lastname: Tyshkevich
authors.forename: Valentina N
authors.initials: VN
authors.lastname: Buneva
authors.forename: Alexey N
authors.initials: AN
authors.lastname: Boiko
authors.forename: Evgenii I
authors.initials: EI
authors.lastname: Gusev
authors.forename: Georgy A
authors.initials: GA
authors.lastname: Nevinsky
authors.forename: Olga O
authors.initials: OO
authors.lastname: Favorova
mesh_terms: D000293:Adolescent; D000328:Adult; D017151:Antibodies, Catalytic / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D006801:Humans; D006868:Hydrolysis; D008297:Male; D008673:Metals, Alkaline Earth / Q000494:pharmacology*; D019216:Metals, Heavy / Q000494:pharmacology*; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood / Q000276:immunology*; D004676:Myelin Basic Protein / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*
chemical_list: D017151:Antibodies, Catalytic; D008673:Metals, Alkaline Earth; D019216:Metals, Heavy; D004676:Myelin Basic Protein