Tendamistat folding

A. Bachman and T. Kiefhaber, Apparent two-state tendamistat folding is a sequential process along a dehned pathway. J. Mol. Biol. 306, 375-386 (2001). 

Thrl67 bond in the cis Prol67Thr TEM-1 /J-lactamase variant is also characterized by a rate constant between 1 x 10-3 s-1 and 4 x 10 3 s-1 for the trans to cis interconversion [26]. Therefore the trans to cis isomerization can be rate-limiting in protein folding under native-like conditions, as was shown for a proline-free variant of the a-amylase inhibitor tendamistat [27]. This seems to be proven in the discovery of a novel protein dass, the secondary amide peptide cis/trans isomerases (APIases), which can accelerate interconversion of these peptide bonds conformers [28],... 

The volume of native Tendamistat is increased by 41.4 + 2.0 cm mol" compared with the denaturated form at pH 2.0 and 35 °C (Fig. 11.2b). This value is virtually independent of the denaturant concentration and it is similar to reaction volumes (AV°) for folding of many other small single-domain proteins [6]. Contributions to AV° may arise from packing deficiencies in the native state as well as from different solvent interactions in the native and in the unfolded protein. Although the reaction volume is virtually independent of the denaturant concentration, the activation volumes for refolding and unfolding both greatly increase with... 

Fig. n.2. (a) Two-state process of the fast folding reaction of the Tendamistat protein. The parameters kf and are the rate constants for the refolding and unfolding... 

---