Abstract
The antitumor antibiotic neocarzinostatin (NSC), isolated from the culture filtrates of Streptomyces carzinostaticus variant F-41 (Ishida et al. 1965), is an acidic single-chain polypeptide with a molecular weight of 10,700 (Meienhofer et al. 1972a). The protein has been purified to homogeneity and its amino acid sequence (Fig. 1) (Meienhofer et al. 1972a, b; Maeda et al. 1974; Samy et al. 1977) and physical properties (Maeda et al. 1973; Samy and Meienhofer 1974) have been determined. There are high degrees of homology of some regions of NCS and the protein antibiotics actinoxanthin (Khokhlov et al. 1969, 1976) and macromomycin (Sawyer et al. 1979). NCS exists in a tight, proteolysis-resistant conformation with an antiparallel β-pleated sheet structure (Samy et al. 1974). It possesses two reduction-resistant disulfide bridges and lacks methionine and histidine. The positions of the disulfides have not yet been unambiguously assigned. NCS contains two tryptophan residues in positions 46 (buried) and 79 and one buried tyrosine residue at position 32. Oxidation of tryptophan 79 does not result in loss of biological activity (Samy et al. 1974). Similarly, acylation of the amino groups (alanine 1 and lysine 20) does not affect the activity of NCS (Maeda 1974; Samy 1977). On the other hand, modification of the carboxyl groups results in loss of activity (Samy 1977). Further, spontaneous deamidation of asparagine 83 at a weakly acidic pH generates “preneocarzinostatin” which lacks biological activity (Maeda and Kuromizu 1977). The chemically deamidated compound is thought to be the same as the material isolated from culture filtrates that antagonizes NCS activity (Kikuchi et al. 1974).
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References
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Goldberg, I.H., Hatayama, T., Kappen, L.S., Napier, M.A. (1980). DNA as a Target for a Protein Antibiotic: Molecular Basis of Action. In: Chapeville, F., Haenni, AL. (eds) Chemical Recognition in Biology. Molecular Biology, Biochemistry and Biophysics, vol 32. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-81503-4_24
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DOI: https://doi.org/10.1007/978-3-642-81503-4_24
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