title: Inactivation of human S-adenosylhomocysteine hydrolase by covalent labeling of cysteine 195 with thionucleoside derivatives.
abstract: A new series of 5'-thioadenosine derivatives 1-4 were synthesized for selectively targeting (195)Cys of human AdoHcy hydrolase. Their incubation with the enzyme resulted in time- and concentration-dependent inactivation, without major modifications of the NAD(+)/NADH ratio. The electrospray mass analysis of the inactivated enzyme with 1, 2, 3, and 4b showed that inhibition was accompanied by the formation of a specific and covalent labeling of each AdoHcy hydrolase subunit. Proteolytic cleavage (endo-Lys-C) and subsequent peptide characterization of the labeled enzyme revealed that (195)Cys was the residue modified during the inactivation process.
authors.affiliation: Laboratoire de Chimie bioorganique, UMR 6519, UFR Sciences, B.P. 1039, 51687 Reims Cedex 2, France.
authors.forename: Georges
authors.initials: G
authors.lastname: Guillerm
authors.forename: Murielle
authors.initials: M
authors.lastname: Muzard
authors.forename: Cédric
authors.initials: C
authors.lastname: Glapski
authors.forename: Serge
authors.initials: S
authors.lastname: Pilard
mesh_terms: D043383:Adenosylhomocysteinase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D003545:Cysteine / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D011480:Protease Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D013872:Thionucleosides / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D011480:Protease Inhibitors; D013872:Thionucleosides; D043383:Adenosylhomocysteinase; D003545:Cysteine