Slow conformational changes in protein folding can be accelerated by enzymes.
In vitro protein folding is a spontaneous process that is driven by a small difference in Gibbs free energy between the native and unfolded states. The information required for correct folding should be entirely encoded in the amino acid sequence of the protein, although increasing evidence exist that proteins participate in cellular folding events. Isomerization of Xaa-Pro peptide bonds is thought to represent some slow steps of folding kinetics. This type of molecular reorganization have to be important in cellular folding due to the different isomeric states in proteins. Peptidyl-prolyl-cis/trans-isomerase (PPIase) catalyzes some, but not all, proline-limited slow folding reactions. On the other hand, the amino acid sequence of 17,8 kD PPIase from pig kidney is identical with cyclophilin (Cyp) that is the major cellular binding protein for the immunosuppressive drug cyclosporin A (CsA). The connection between enzyme catalyzed cis/trans isomerization, protein folding and immunosuppression is still unknown. PPIases of the cyclophilin type are found in most organisms and in various subcellular compartments. Recently a second family of PPIases has been discovered. These small proteins are structurally related to the cyclophilins; yet they bind with a high affinity to another immunosuppressive drug, the macrolide FK 506. Although it seems to be logical to ascribe the enzymatic activity of these proteins to a catalytic role in the folding of proteins within the cell other possibilities must also be considered and are discussed.
Bang
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H
Martin-Luther-Universität Halle-Wittenberg, Institut für Biochemie.
Fischer
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G
D000591:Amino Acid Isomerases / Q000737:chemistry / Q000276:immunology; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry / Q000276:immunology; D007166:Immunosuppressive Agents / Q000737:chemistry; D007700:Kinetics; D019696:Peptidylprolyl Isomerase; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry*; D013237:Stereoisomerism
D002352:Carrier Proteins; D007166:Immunosuppressive Agents; D011506:Proteins; D000591:Amino Acid Isomerases; D019696:Peptidylprolyl Isomerase