Understanding base and backbone contributions of phosphorothioate DNA for molecular recognition with SBD proteins.

Bacterial DNA phosphorothioate (PT) modification provides a specific anchoring site for sulfur-binding proteins (SBDs). Besides, their recognition patterns include phosphate links and bases neighboring the PT-modified site, thereby bringing about genome sequence-dependent properties in PT-related epigenetics. Here, we analyze the contributions of the DNA backbone (phosphates and deoxyribose) and bases bound with two SBD proteins in and ( and ). The chalcogen-hydrophobic interactions remained constantly at the anchoring site while the adjacent bases formed conditional and distinctive non-covalent interactions. More importantly, SBD/PT-DNA interactions were not limited within the traditional "4-bp core" range from 5'-I to 3'-III but extended to upstream 5'-II and 5'-III bases and even 5''-I to 5''-III at the non-PT-modified complementary strand. From the epigenetic viewpoint, bases 3'-II, 5''-I, and 5''-III of and 3'-II, 5''-II, and 5''-III of present remarkable differentiations in the molecular recognitions. From the protein viewpoint, H102 in and R191 in contribute significantly while proline residues at the PT-bound site are strictly conserved for the PT-chalcogen bond. The mutual and make-up mutations are proposed to alter the /PT-DNA recognition pattern, besides additional chiral phosphorothioate modifications on phosphates 5'-II, 5'-II, 3'-I, and 3'-II.