A tri-functional monomeric primase–polymerase domain encoded by the plasmid pIT3 fromSulfolobus solfataricusstrain IT3 was identified using a structural–functional approach. The N-terminal domain of the pIT3 repli-cation protein encompassing residues 31–245 (. Rep245) was modeled onto the crystallographic structure of the bifunctional primase–polymerase domain of the archaeal plasmid pRN1 and refined by molecular dynamics in solution.