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Three‐dimensional structure and actions of immunosuppressants and their immunophilins
Author(s) -
Braun Werner,
Kallen Joerg,
Mikol Vincent,
Walkinshaw Malcolm D.,
Wüthrich Kurt
Publication year - 1995
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.9.1.7529736
Subject(s) - fkbp , calcineurin , context (archaeology) , chemistry , peptidylprolyl isomerase , pharmacology , biochemistry , biology , enzyme , medicine , transplantation , paleontology , isomerase
The use of the immunosuppressant drug cyclosporin A (CsA) as a biochemical tool to study the signal transduction pathway in T cells has led to the discovery of a first family of immunosuppressant‐binding proteins or “immunophilins,” the cyclophilins (Cyp). Another, chemically unrelated immunosuppressant molecule, FK506, was then found to be related to a second class of immunophilins, the FK506‐binding proteins (FKBPs), This paper reviews the existing structural information on these immunophilins in the context of present knowledge of the biochemical mechanisms for immunosuppression. The formation of Cyp‐CsA and FKBP‐FK506 complexes, and the subsequent specific interaction of these complexes with the serine/threonine phosphatase calcineurin (CN), are key steps in the cascade of events that result in the desired immunosuppression. Knowledge of the conformation of the Cyp‐CsA‐CN and FKBP‐FK506‐CN ternary complexes is of significant biomedical interest, because mimics of the composite contact surfaces of, for example, Cyp‐CsA or FKBP‐FK506, could provide immunosuppressant drugs with improved pharmacological profiles.—Braun, W., Kallen, J., Mikol, V., Walkinshaw, M. D., Wüthrich, K. Three‐dimensional structure and actions of immunosuppressants and their immunophilins. FASEB J. 9, 63‐72 (1995)