InterPro domain: IPR002186

This family is comprised of antitumour antibiotic chromoproteins, as represented by neocarzinostatin [ 1 ]. These chromoproteins consist of a noncovalently bound, labile enediyne chromophore and its stabilising carrier apoprotein. The protein component of the chromophore displays an unusual bicyclic dienediyne structure. The chromoprotein inter-chelates the DNA, where its cycloaromatisation produces a biradical intermediate that has the ability to abstract hydrogens from the sugar moiety of DNA. This causes single- and double-strand breaks in the DNA [ 2 ]. In addition to their ability to cleave DNA at sites specific for each chromophore, results indicate that these chromoproteins also possess proteolytic activity against histones, with histone H1 as the preferred substrate [ 3 ].

Neocarzinostatin has 2 disulphide bridges and is kidney-shaped with 2 defined domains that hold a binding cavity. The larger domain forms a 7-stranded antiparallel beta-barrel and the smaller domain consists of 2 anti-parallel strands of beta sheet that are perpendicular to each other [ 4 ]. Other members of this family include macromycin, actinoxanthine, kedarcidin [ 4 ], and C-1027 [ 4 ].

1. Crystal structure of neocarzinostatin, an antitumor protein-chromophore complex. Science 262, 1042-6
2. Solution structures of C-1027 apoprotein and its complex with the aromatized chromophore. J. Mol. Biol. 309, 267-83
3. The proteolytic specificity of the natural enediyne-containing chromoproteins is unique to each chromoprotein. Chem. Biol. 2, 451-5