2R2S

Co(III)bleomycinB2 bound to d(ATTAGTTATAACTAAT) complexed with MMLV RT catalytic fragment

2R2S の概要

• エントリーDOI: 10.2210/pdb2r2s/pdb
• 関連するPDBエントリー: 2R2R 2R2T 2R2U
• 分子名称: DNA (5'-D(*DAP*DTP*DTP*DAP*DGP*DTP*DT)-3'), DNA (5'-D(P*DTP*DAP*DAP*DCP*DTP*DAP*DAP*DT)-3'), Reverse transcriptase, ... (6 entities in total)
• 機能のキーワード: bleomycin, drug-dna complex, protein-dna complex, mmlv rt, dna integration, dna recombination, endonuclease, multifunctional enzyme, nuclease, nucleotidyltransferase, rna-directed dna polymerase, transferase, transferase-dna complex, transferase/dna
• 由来する生物種: Moloney murine leukemia virus (MoMLV)
• 細胞内の位置: Gag-Pol polyprotein: Host cell membrane ; Lipid-anchor . Matrix protein p15: Virion . Capsid protein p30: Virion . Nucleocapsid protein p10: Virion : P03355
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 34956.80

構造登録者

Goodwin, K.D.,Lewis, M.A.,Long, E.C.,Georgiadis, M.M. (登録日: 2007-08-27, 公開日: 2008-07-22, 最終更新日: 2024-02-21)

主引用文献

Goodwin, K.D.,Lewis, M.A.,Long, E.C.,Georgiadis, M.M.
Crystal structure of DNA-bound Co(III) bleomycin B2: Insights on intercalation and minor groove binding.
Proc.Natl.Acad.Sci.Usa, 105:5052-5056, 2008

PubMed Abstract: Bleomycins constitute a widely studied class of complex DNA cleaving natural products that are used to treat various cancers. Since their first isolation, the bleomycins have provided a paradigm for the development and discovery of additional DNA-cleaving chemotherapeutic agents. The bleomycins consist of a disaccharide-modified metal-binding domain connected to a bithiazole/C-terminal tail via a methylvalerate-Thr linker and induce DNA damage after oxygen activation through site-selective cleavage of duplex DNA at 5'-GT/C sites. Here, we present crystal structures of two different 5'-GT containing oligonucleotides in both the presence and absence of bound Co(III).bleomycin B(2). Several findings from our studies impact the current view of bleomycin binding to DNA. First, we report that the bithiazole intercalates in two distinct modes and can do so independently of well ordered minor groove binding of the metal binding/disaccharide domains. Second, the Co(III)-coordinating equatorial ligands in our structure include the imidazole, histidine amide, pyrimidine N1, and the secondary amine of the beta aminoalanine, whereas the primary amine acts as an axial ligand. Third, minor groove binding of Co(III).bleomycin involves direct hydrogen bonding interactions of the metal binding domain and disaccharide with the DNA. Finally, modeling of a hydroperoxide ligand coordinated to Co(III) suggests that it is ideally positioned for initiation of C4'-H abstraction.

PubMed: 18362349
DOI: 10.1073/pnas.0708143105

実験手法

X-RAY DIFFRACTION (2.8 Å)