SOLUTION CONFORMATION OF A CYCLOPHILIN-BOUND PROLINE ISOMERASE SUBSTRATE

Cyclophilin (CyP) is the 17.8-kDa cytosolic receptor of the immunosupp ressant cyclosporin A (CsA) and also a peptidyl prolyl cis-trans isome rase (PPIase). In order to gain insights into the PPIase mechanism, tr ansferred nuclear Overhauser effect (TRNOE) measurements by two-dimens ional H-1 NMR were used to determine the conformation of the isomerase -bound standard model substrate suc-AAPF-pNA. Results indicate a cis-l ike conformation for the CyP-bound substrate with the A-P peptide bond being no more than 40 degrees out of planarity.