Crystal structure of neocarzinostatin, an antitumor protein-chromophore complex.
Structures of the protein-chromophore complex and the apoprotein form of neocarzinostatin were determined at 1.8 angstrom resolution. Neocarzinostatin is composed of a labile chromophore with DNA-cleaving activity and a stabilizing protein. The chromophore displays marked nonlinearity of the triple bonds and is bound noncovalently in a pocket formed by the two protein domains. The chromophore pi-face interacts with the phenyl ring edges of Phe52 and Phe78. The amino sugar and carbonate groups of the chromophore are solvent exposed, whereas the epoxide, acetylene groups, and carbon C-12, the site of nucleophilic thiol addition during chromophore activation, are unexposed. The position of the amino group of the chromophore carbohydrate relative to C-12 supports the idea that the amino group plays a role in thiol activation.
Kim
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KH
Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena 91125.
Kwon
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BM
Myers
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Rees
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D001059:Apoproteins / Q000737:chemistry; D003196:Computer Graphics; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D006860:Hydrogen Bonding; D008958:Models, Molecular; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D009353:Zinostatin / Q000737:chemistry*
D001059:Apoproteins; D009353:Zinostatin