title: The esterase-like activity of covalently bound human third complement protein.
abstract: The acyl ester bond between the third complement protein, C3, and a variety of molecules is hydrolyzed spontaneously at neutral pH (Venkatesh et al., 1984). Modification of the free, single sulfhydryl group of bound C3 by thiol reagents suggested that a functional group other than the -SH acts as a "catalytic" group in this intramolecular hydrolytic reaction. Complete inhibition of the esterase-like activity is observed with stoichiometric amounts of mercuric chloride, palladium chloride, and the bifunctional organic mercurial, 3,6-bis-(acetoxymercuri)-o-toluidine [BAMT]. Since alkyl and aryl mercuric ions do not inhibit the esterase-like activity of C3-[3H]glycerol, it is conjectured that divalent mercury, palladium, and BAMT will form a complex with the -SH group and an atom of the "catalytic" group X having a lone pair of electrons. The structural features of C3 that are essential for the esterase-like activity remain intact after subjecting C3-[3H]glycerol to covalent chromatography on organomercurial agarose. Based on the observed effects of chemical reagents and the kinetic deuterium solvent isotope effect on the esterase-like activity, a general-base mechanism is proposed for the intramolecular hydrolysis of the acyl ester bond in covalently bound C3. The "catalytic" group X is located in the C3d region (residues 317-632 of the alpha chain), since C3d-[3H]glycerol also has esterase-like activity. A general-base mechanism mediated by the same "catalytic" group X may also apply to the formation of acyl ester bonds following the hydrolysis of the internal thiolester bond in native C3.
authors.affiliation: Department of Genetics, Washington University School of Medicine, St. Louis, MO 63110.
authors.forename: Y P
authors.initials: YP
authors.lastname: Venkatesh
authors.forename: R P
authors.initials: RP
authors.lastname: Levine
mesh_terms: D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002847:Chromatography, Agarose; D003176:Complement C3 / Q000276:immunology*; D015933:Complement C3d; D003903:Deuterium; D004950:Esterases / Q000276:immunology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008670:Metals / Q000494:pharmacology; D011480:Protease Inhibitors / Q000494:pharmacology
chemical_list: D003176:Complement C3; D008670:Metals; D011480:Protease Inhibitors; D015933:Complement C3d; D003903:Deuterium; D004950:Esterases