THE EFFECT OF THE L-AZETIDINE-2-CARBOXYLIC ACID RESIDUE ON PROTEIN CONFORMATION .4. LOCAL SUBSTITUTIONS IN THE COLLAGEN TRIPLE-HELIX

The properties of collagen are affected by the replacement of Pro by i mino acid analogues. The structural effect of the low-level local subs titution of L-azetidine-2-carboxylic acid (Aze) has been analyzed by c omputing the energy of CH3CO- (Gly-Pro-Pro)4-NHCH3 triple helices in w hich a single residue of one strand has been replaced by Aze. When Aze is in position Y of a (Gly-X-Y) unit, low-energy local deformations a re introduced in the triple helix, i.e., it becomes more flexible. On the other hand, the flexibility of the triple helix is not increased w ith Aze in position X. The energy of the triple helix to coil transiti on is not changed significantly by this amount of substitution. In an earlier study, we have demonstrated that the regular substitution of A ze in every tripeptide distorts or destabilizes the triple helix to a large extent [A. Zagari, G. Nemethy, & H. A. Scheraga (1990) Biopolyme rs, Vol. 30, pp. 967-974]. Thus, it appears that a high level of subst itution is required to cause the observed chemical and biological effe cts of Aze on collagen. (C) 1994 John Wiley & Sons, Inc.