The importance of fitting in: conformational preference of selenium 2′ modifications in nucleosides and helical structures

Selenomethionine incorporation has proven useful in X-ray crystallography of proteins to obtain phase information. In nucleic acids, the introduction of selenium to different positions is beneficial for solving the phase problem as well, but its addition to the 2′ position also significantly enhances the crystal formation. The selenium modification in a single nucleotide shows a preference towards 2′-endo sugar puckering, which is in conflict with existing crystal structures where the duplex incorporated 2′-selenium-modified nucleotide is exclusively found in a 3′-endo conformation. Our work provides a rationale why 2′-selenium modifications facilitate crystallization despite this contradictory behavior.