An antitumor polypeptide antibiotic neocarzinostatin: the mode of apo-protein--chromophore interaction.
The mode of neocarzinostatin-chromophore (NCS-chr)-apo-neocarzinostatin (apo-NCS) interaction in neocarzinostatin (NCS) complex has been described. The NCS-chr release from the NCS complex in the presence of various reagents, which destroy the high-order structure of the protein under various pH conditions, was examined. We found that (i) sodium dodecylsulfate, Nonidet P 40, 8 M urea, and 2-propanol did release NCS-chr from NCS, (ii) no NCS-chr release is detected below pH 7, but it is enhanced at high pH and (iii) beta-naphthol as a model of naphthalenecarboxylic acid derivative and D-galactosamine as a model of N-methylfucosamine of NCS-chr did release NCS-chr from NCS. These observations indicate that the binding of NCS-chr to apo-NCS may be due to not only ionic interaction between the acidic side chain of apo-NCS and the basic center of an aminosugar moiety of NCS-chr but also hydrophobic interaction between the hydrophobic amino acids of apo-NCS and hydrophobic moieties of NCS-chr. Apo-NCS is a very hydrophilic protein, since it has an high hydrophilic amino acid content. So, local hydrophobicity, local hydrophilicity and secondary structure of apo-NCS were predicted. Hydrophobic residues of apo-NCS predominantly located in beta-sheet structures near the carboxyl-terminus. These predictions are in good agreement with the results suggesting that NCS-chr bound carboxyl-terminal-43-peptide of apo-NCS in our previous result.
Edo
K
K
Department of Pharmaceutical Sciences, Tohoku University Hospital, Sendai, Japan.
Saito
K
K
Akiyama-Murai
Y
Y
Mizugaki
M
M
Koide
Y
Y
Ishida
N
N
D000595:Amino Acid Sequence; D000903:Antibiotics, Antineoplastic / Q000032:analysis*; D001059:Apoproteins / Q000032:analysis*; D053281:Enediynes; D005453:Fluorescence; D008969:Molecular Sequence Data; D011489:Protein Denaturation; D009353:Zinostatin / Q000031:analogs & derivatives / Q000032:analysis*
D000903:Antibiotics, Antineoplastic; D001059:Apoproteins; D053281:Enediynes; C052401:aponeocarzinostatin; C032372:neocarzinostatin chromophore; D009353:Zinostatin