Enzymatic Activity of the Rotamases

More than 20 FKBPs and at least 30 cyclophilins have been identified in recent years. New PPIases continue to be discovered with each passing year. We will focus on the better known and characterized immunophilins in mammals and their relevance to pharmaceutical research. We will briefly discuss the enzymatic activities and cellular locations of the major FKBPs and cyclophilins, and then move on to a detailed discussion of the structural biology of the immunophilins. 

By convention, members of the FKBP family are named by appending to the prefix FKBP the apparent weight of the protein in kilodaltons. Thus 

Cyclophilin A itself is a catalytically efficient enzyme, with a measured kcJKm of 10 pM s 1 with the substrate tetrapeptide succinyl-Ala-Ala-Pro-Phe-pNA. It shows little selectivity towards residues in the PI position, however. Harrison and Stein assayed a number of tetrapeptides as substrates for cyclophilin A and FKBP12 67 Very little selectivity towards Xaa was found in the series succ-Ala-Xaa-Pro-Phe-pNA, except for a general preference for a hydrophobic PI residue and a slight preference for Ala over others. In contrast, FKBP12 evinces a marked preference for branched alkyl residues at PI, particularly preferring leucine. 

The mechanism whereby the rotamases catalyze the interconversion of amide bond rotamers has been a source of considerable interest. It was 

FKBP25 FKBP38 25,325 160 (FK506) 0.9 (rapamycin) 4.5 (FK506) 0.8 (rapamycin) 0.8 [b] Cytosol, nucleus 48, 49 50 2 FKBP domains, 1 CyP domain 

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