Cover Picture: Exploiting the Substrate Tolerance of Farnesyltransferase for Site-Selective Protein Derivatization (ChemBioChem 4/2007) (page 365)
Uyen T. T. Nguyen, Janina Cramer, Joaquin Gomis, Reinhard Reents, Marta Gutierrez-Rodriguez, Roger S. Goody, Kirill Alexandrov and Herbert Waldmann
Article first published online: 19 FEB 2007 | DOI: 10.1002/cbic.200790007
The cover picture shows the crystal structure of farnesyltransferase (FTase), which recognizes a short cysteine-containing C-terminal sequence (CAAX box) on its substrates. The enzyme transfers a farnesyl moiety that is harbored in a hydrophobic pocket onto the cysteine of the CAAX box. FTase is an efficient protein-derivatization tool as it modifies virtually any recombinant protein containing a C-terminally grafted CAAX box. Moreover, it tolerates modifications in the scaffold of its lipid substrate; this was explored for the incorporation of functional groups. The enzyme prenylates CAAX box-tagged proteins with azide and diene groups containing isoprenoids quantitatively. These modifications do not change the functionality or the folding of the test proteins. The functional groups on the isoprenoid analogues can then further serve as anchor points for chemical derivatization both by Staudinger ligation and by Diels–Alder cycloaddition. Further details can be found in the article by K. Alexandrov, H. Waldmann, et al. on p. 408 ff.