Population shift vs induced fit: the case of bovine seminal ribonuclease swapping dimer.

Bovine seminal RNase (BS-RNase) is a unique member of the pancreatic-like RNase superfamily. This enzyme exists as two conformational isomers with distinctive biol. properties. The structure of the major isomer is characterized by the swapping of the N-terminal segment (M´M BS-RNase). In this article, the crystal structures of the ligand-free M´M BS-RNase and its complex with 2'-deoxycitidylyl(3',5')-2'-deoxyadenosine derived from isomorphous crystals have been refined. Interestingly, the comparison between this novel ligand-free form and the previously published sulfate-bound structure reveals significant differences. In particular, the ligand-free M´M BS-RNase is closer to the structure of M´M BS-RNase productive complexes than to the sulfate-bound form. These results reveal that M´M BS-RNase presents a remarkable flexibility, despite the structural constraints of the interchain disulfide bridges and the swapping of the N-terminal helixes. These findings have important implications to the ligand binding mechanism of M´M BS-RNase. Indeed, a population shift rather than a substrate-induced conformational transition may occur in the M´M BS-RNase ligand binding process.