This review describes some features of the detailed structure-function relationship in two extremophilic model proteins, the translation elongation factors SsEF–1α and SsEF–2 isolated from the hyperthermophilic archaeon Sulfolobus solfataricus. The data reported describe the effect of typical inhibitors of the corresponding eubacterial EF–Tu and EF–G on the multiple reactions supported by SsEF–1<SPAN AR-SA mso-bidi-language: EN-US; mso-fareast-language: mso-ansi-language: Roman`; New `Times mso-fareast-font-family: 11.0pt; mso-bidi-font-size: FONT-FAMILY: 12pt; DESIGNTIMESP=26967>α and SsEF–2 during the fulfilment of their functions. The  comparison with the properties of other bacterial or eukaryal  factors  allows  a  philogenetic  relationship of the peptide elongation cycle in the three living domains.

SsEF–1α is able to interact with typical eubacterial protein synthesis inhibitors, such as the antibiotic kirromycin and GE2270A. In particular, kirromycin improves the intrinsic GTPase of some mutant forms of the archaeal factor, whereas GE2270A inhibits both the intrinsic and the ribosome–dependent GTPase of wild–type SsEF–1α. The analysis of the behaviour of engineered forms of the archaeal factor proved that GE2270A interacts mainly with the middle domain of SsEF–1α.

Also  SsEF–2  interacts  with   typical inhibitors of the eubacterial EF–G. In fact, the steroid antibiotics fusidic  and  helvolic  acid  are able to inhibit poly (Phe) synthesis and the ribosome–dependent GTPase of SsEF–2. A mutant form of SsEF–2 exhibited an increased sensitivity to these antibiotics, thus allowing to detect a fusidane responsiveness even in the absence of ribosome. This latter feature could indicate that the archaeal SsEF–2 harbors the structural requirements for the interaction with fusidane antibiotics.