title: Intersubunit interactions in human cytidine deaminase.
abstract: In order to design new efficient cytidine based drugs, an intersubunit interactions study related to the active site has been performed on the wild-type cytidine deaminase (CDA) and on the mutant enzyme F137W/W113F. F137 is the homologous to the Bacillus subtilis CDA F125 involved in the subunit interactions. In presence of the dissociating agent SDS, wild-type human CDA dissociate into enzymatically inactive monomers without intermediate forms via a non-cooperative transition. Extensive dialysis or dilution of the inactivated monomers restores completely the activity. The presence of the strong human CDA competitive inhibitor 5-fluorozebularine disfavour dissociation of the tetramer into subunits in the wild-type CDA but not in mutant enzyme F137W/W113F.
authors.affiliation: Dipartimento di Scienze Veterinarie, University of Camerino, Matelica (MC), Italy.
authors.forename: S
authors.initials: S
authors.lastname: Vincenzetti
authors.forename: S
authors.initials: S
authors.lastname: Costanzi
authors.forename: G
authors.initials: G
authors.lastname: Cristalli
authors.forename: P
authors.initials: P
authors.lastname: Mariani
authors.forename: B
authors.initials: B
authors.lastname: Quadrini
authors.forename: N
authors.initials: N
authors.lastname: Cammertoni
authors.forename: A
authors.initials: A
authors.lastname: Vita
mesh_terms: D019943:Amino Acid Substitution; D001412:Bacillus subtilis / Q000201:enzymology; D002850:Chromatography, Gel; D003564:Cytidine Deaminase / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D016297:Mutagenesis, Site-Directed; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism
chemical_list: D021122:Protein Subunits; D011994:Recombinant Proteins; D003564:Cytidine Deaminase