Base recognition mechanism of bleomycin: solution structure of d(GGGGAGCTCCCC)2 based on 1H-NMR and restrained molecular dynamics.
The self-complementary d(GGGGAGCTCCCC) dodecanucleotide cleavage by bleomycin occurs at G(4)pA(5) site rather than G(6)pC(7) site which is known as the preferential sequence. The molecular structure of this dodecamer is observed as the distorted B-DNA by the CD spectra and proton NMR measurements. Three-dimensional structures in solution evaluated by molecular dynamics calculations with inter proton distance restraints have the distorted form of the minor groove structure at G(6)pC(7) site. These evidences offer the recognition mechanism model of the DNA base sequence by bleomycin.
Hiroaki
H
H
Faculty of Pharmaceutical Sciences, Osaka University, Japan.
Ebata
T
T
Uesugi
S
S
Fujii
S
S
D001483:Base Sequence; D001761:Bleomycin / Q000378:metabolism*; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D009838:Oligodeoxyribonucleotides / Q000737:chemistry / Q000378:metabolism*; D012996:Solutions
D009838:Oligodeoxyribonucleotides; D012996:Solutions; D001761:Bleomycin; D004247:DNA