title: Computer modeling analysis for enediyne chromophore-apoprotein complex of macromolecular antitumor antibiotic C-1027.
abstract: On the basis of the van der Waals and electrostatic potential energy calculations and energy minimization (EM), a model for the apoprotein-chromophore complex of C-1027 has been constructed by docking the apoprotein (Apo-C1027) and the chromophore (C1027-Chr). The model of the apoprotein-chromophore complex also suggests the most probable stereochemistry of the chromophore (8R,9S,13R,17R), specific interactions between Apo-C1027 and C1027-Chr, and the origin of the stabilization of the chromophore by the apoprotein. The acetylenic bond of C1027-Chr appears to be stabilized by (1) hydrophobic interactions with the bottom of the pocket of Apo-C1027, (2) orbital interaction with Cys36-Cys45 disulfide bond, (3) van der Waals contact with Pro76, and (4) pi-pi stacking with the benzene moiety of the chromophore. In this model, molecular dynamics (MD) simulation of the chromophore indicates that the acetylene bond distance (C2-C7) of the apoprotein-bound chromophore is longer than that of the unbound chromophore.
authors.affiliation: Institute for Chemical Research, Kyoto University, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Okuno
authors.forename: M
authors.initials: M
authors.lastname: Otsuka
authors.forename: Y
authors.initials: Y
authors.lastname: Sugiura
mesh_terms: D000595:Amino Acid Sequence; D000617:Aminoglycosides; D000900:Anti-Bacterial Agents / Q000737:chemistry*; D000903:Antibiotics, Antineoplastic / Q000737:chemistry*; D001059:Apoproteins / Q000737:chemistry*; D001665:Binding Sites; D002863:Chromogenic Compounds / Q000737:chemistry*; D003196:Computer Graphics; D003198:Computer Simulation; D053281:Enediynes; D008969:Molecular Sequence Data; D010455:Peptides; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D000903:Antibiotics, Antineoplastic; D001059:Apoproteins; D002863:Chromogenic Compounds; D053281:Enediynes; D010455:Peptides; C058024:C 1027