Prolyl Isomerizations in Folded Proteins

In crystal structures of folded proteins the prolyl peptide bonds are generally either cis or trans in every molecule. There is, however, an increasing number of exceptions to this rule, and cis/trans equilibria have been found, in particular by 2D-NMR spectroscopy in solution. Examples include staphylococcal nuclease (Evans et al, 1987), insulin (Higgins etal., 1988), calbindin (Chazin et al., 1989 Kordel et al., 1990), scorpion venom Lqh-8/6 (Adjadj et al., 1997), human interleukin-3 (Feng et al., 1997), and the TB6 domain of human fibrillin-1 (Yuan etal., 1997 Yuan et al., 1998). 

The hyperactive variant SC-55494 of human interleukin-3 (hIL-3) shows at least two major conformations (Wu and Raleigh, 1998). This heterogeneity and the activity were unchanged in variants with single 

---