9: J Biol Inorg Chem 2003 Mar 12; [epub ahead of print]
The solution structure of the Ga(III)- bleomycin A2
complex resolved by NMR and molecular modeling; interaction with d(CCAGGCCTGG).
Papakyriakou A, Mouzopoulou B, Katsaros N.
Institute of Physical Chemistry, NCSR "Demokritos", 153-10 Ag. Paraskevi Attikis,
The solution structure of the Ga(III)- bleomycin A2 complex (Ga bleomycin M) has been
determined using 2D NMR methods in combination with molecular dynamics
calculations. Complete assignment of the amide and amine protons, observation of
80 NOEs and measurement of 15 (3)JH(-H) coupling constants provided us with a
well-defined structure using a restrained simulated annealing protocol. On the
basis of distance and dihedral angle constraints agreement, along with potential
energy considerations, the favored model is a five-coordinate complex with the
primary amine of beta-aminoalanine holding the axial position of a distorted
tetragonal pyramid. The disaccharide moiety of GaBLM is not a ligand, sharing
the same side of the equatorial plane with the axial amine ligand. Titration of
the self-complementary oligonucleotide d(CCAGGCCTGG) with GaBLM results in the
formation of only one 1:1 complex in slow exchange on the NMR time scale. Our
data indicate that the bithiazole moiety intercalates between the C6*G15 and
C7*G14 base pairs, in a similar mode to that reported by earlier studies.
Structural implications and comparisons to other metallo-bleomycins are