CRYSTAL-STRUCTURE OF APO-NEOCARZINOSTATIN AT 0.15-NM RESOLUTION

The three-dimensional structure of apo-neocarzinostatin, an antitumour - antibiotic protein isolated from Streptomyces carzinostaticus, has b een determined by X-ray diffraction at 0.15-nm resolution and refined to R = 17.2%. The crystal structure of neocarzinostin is similar to th at of the related proteins actinoxanthin and macromomycin. It is also in good agreement with the solution structure determined by NMR spectr oscopy. The protein molecule consists of a seven-stranded antiparallel beta-sandwich and a smaller lobe formed by two beta-ribbons. A deep c left between the two lobes is a putative chromophore binding site. Sid e chains of Trp39, Leu45, Phe5-, Phe78 and the disulphide Cys37-Cys47 aligning the binding cleft in neocarzinostatin suggest the importance of hydrophobic interactions in stabilizing the chromophore molecule. C omparison of the atomic models of neocarzinostatin, actinoxanthin and macromomycin reveals functional residues which might determine specifi city towards different chromophores.