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Neocarzinostatin: Selective tryptophan oxidation and neocarzinostatin-chromophore binding to apo-neocarzinostatin
- Source :
- Chemical and Pharmaceutical Bulletin. 39:170-176
- Publication Year :
- 1991
- Publisher :
- Pharmaceutical Society of Japan, 1991.
-
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.
- Subjects :
- Stereochemistry
Molecular Sequence Data
behavioral disciplines and activities
Streptomyces
Residue (chemistry)
Zinostatin
mental disorders
Drug Discovery
medicine
Amino Acid Sequence
Binding site
Neocarzinostatin
biology
Streptomycetaceae
Chemistry
Tryptophan
General Chemistry
General Medicine
Chromophore
biology.organism_classification
Fluorescence
lipids (amino acids, peptides, and proteins)
Apoproteins
Oxidation-Reduction
Protein Binding
medicine.drug
Subjects
Details
- ISSN :
- 13475223 and 00092363
- Volume :
- 39
- Database :
- OpenAIRE
- Journal :
- Chemical and Pharmaceutical Bulletin
- Accession number :
- edsair.doi.dedup.....a64f51d5d78f01284157f229cb9ed7bc