Lysines of histone 1 represent the principal target for covalent binding of microsomally activated benzo[a]pyrene in vitro.
The principal target amino acid residue for covalent binding of metabolically activated [3H]benzo[a]pyrene (B[a]P) to histone 1 (H1) has been identified. Highly purified calf thymus H1 was modified by incubation with [3H]B[a]P in the presence of rat liver microsomes. The relative distribution of [3H]B[a]P versus specific amino acids among the N-bromo-succinimide peptides of H1 suggested that lysine may be the target. This was tested by selectively blocking the nucleophilic amino groups of lysine by amidination prior to [3H]B[a]P binding. Increasing levels of amidination of H1 resulted in corresponding decreases in the reactivity of this histone toward [3H]B[a]P. Amidination of 93% of the lysines blocked 87% of the [3H]B[a]P binding indicating that lysine was the principal target. N-terminal amino acid sequencing of [3H]B[a]P-modified H1 confirmed that lysine residues had bound [3H]B[a]P.
D001580:Benzopyrenes / Q000378:metabolism*; D001711:Biotransformation; D002942:Circular Dichroism; D006657:Histones / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism; D008862:Microsomes, Liver / Q000378:metabolism; D011487:Protein Conformation
D001580:Benzopyrenes; D006657:Histones; D008239:Lysine