A model for the activation and inactivation of neocarzinostatin, an antitumor protein.
Sulfhydryl compounds specifically activate and inactive neocarzinostatin as measured by the in vitro strand scission of T2 DNA. This effect, and evidence for strained disulfides in the molecule, leads us to propose a model of activation and inactivation. We suggest that neocarzinostatin reacts with sulfhydryl reagents to produce a short-lived active form which may react with DNA or proceed irreversibly via a conformational change to an inactive form (preneocarzinostatin). Three parameters of neocarzinostatin activity (inactivation rate, single strand break plateau position, and initial single strand break rate), have been measured for various sulfhydryl concentrations, and the observed results agree well with values expected from a simplified mathematical treatment of the model, thus supporting the assumptions made.
D000903:Antibiotics, Antineoplastic; D004279:DNA, Viral; D007700:Kinetics; D009690:Nucleic Acid Conformation; D011485:Protein Binding; D011487:Protein Conformation; D013438:Sulfhydryl Compounds; D013604:T-Phages; D009353:Zinostatin
D000903:Antibiotics, Antineoplastic; D004279:DNA, Viral; D013438:Sulfhydryl Compounds; D009353:Zinostatin