title: Neocarzinostatin: selective tryptophan oxidation and neocarzinostatin-chromophore binding to apo-neocarzinostatin.
abstract: Neocarzinostatin (NCS), an antitumor protein antibiotic, is composed of apo-neocarzinostatin (apo-NCS) and neocarzinostatin-chromophore (NCS-chr), the principle of the biological activities of NCS. Apo-NCS having two tryptophan (Trp) residues at positions (39 and 83) was chemically modified by N-bromosuccinimide in a study on the correlation of the binding site(s) of NCS-chr. Selective oxidation of Trp residues was observed when NCS was titrated with N-bromosuccinimide. In contrast, non-selective oxidation of the two Trps on apo-NCS was observed and both Trp (39 and 83) of apo-NCS were titrated with N-bromosuccinimide. After selective oxidation, the remaining Trp residue of NCS was assigned as Trp (83). These results clearly indicate that the Trp (83) residue of apo-NCS changed from the "reactive type" to the "non-reactive type" after the binding of NCS-chr with apo-NCS. The fluorescence emission intensity of apo-NCS generated from the Trp (39) residue was quenched by NCS-chr. These data suggest that NCS-chr directly interacts with the Trp (39) residue and that a beta-sheeted loop containing the Trp (83) residue of apo-NCS changes the high-order structure upon binding with NCS-chr.
authors.affiliation: Department of Pharmaceutical Sciences, Tohoku University Hospital, Sendai, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Edo
authors.forename: K
authors.initials: K
authors.lastname: Saito
authors.forename: Y
authors.initials: Y
authors.lastname: Matsuda
authors.forename: Y
authors.initials: Y
authors.lastname: Akiyama-Murai
authors.forename: M
authors.initials: M
authors.lastname: Mizugaki
authors.forename: Y
authors.initials: Y
authors.lastname: Koide
authors.forename: N
authors.initials: N
authors.lastname: Ishida
mesh_terms: D000595:Amino Acid Sequence; D001059:Apoproteins / Q000378:metabolism; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D011485:Protein Binding; D014364:Tryptophan / Q000378:metabolism*; D009353:Zinostatin / Q000378:metabolism*
chemical_list: D001059:Apoproteins; D014364:Tryptophan; D009353:Zinostatin