Three-dimensional structure actions of immunosuppressants and their immunophilins

Werner Braun, Joerg Kallen, Vincent Mikol, Malcolm D. Walkinshaw, Kurt Wüthrich

Research output: Contribution to journalArticle

86 Citations (Scopus)

Abstract

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-FK.506-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.

Original languageEnglish (US)
Pages (from-to)63-72
Number of pages10
JournalFASEB Journal
Volume9
Issue number1
StatePublished - 1995
Externally publishedYes

Fingerprint

Immunophilins
Tacrolimus Binding Proteins
Cyclophilins
immunosuppressive agents
cyclophilins
Immunosuppressive Agents
cyclosporine
Cyclosporine
binding proteins
Calcineurin
Tacrolimus
Immunosuppression
immunosuppression
Signal transduction
T-cells
Phosphoprotein Phosphatases
drugs
biochemical mechanisms
Pharmaceutical Preparations
Conformations

Keywords

  • Cyclophilin
  • Cyclosporin A
  • FK506
  • FKBP
  • Rapamycin

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this

Braun, W., Kallen, J., Mikol, V., Walkinshaw, M. D., & Wüthrich, K. (1995). Three-dimensional structure actions of immunosuppressants and their immunophilins. FASEB Journal, 9(1), 63-72.

Three-dimensional structure actions of immunosuppressants and their immunophilins. / Braun, Werner; Kallen, Joerg; Mikol, Vincent; Walkinshaw, Malcolm D.; Wüthrich, Kurt.

In: FASEB Journal, Vol. 9, No. 1, 1995, p. 63-72.

Research output: Contribution to journalArticle

Braun, W, Kallen, J, Mikol, V, Walkinshaw, MD & Wüthrich, K 1995, 'Three-dimensional structure actions of immunosuppressants and their immunophilins', FASEB Journal, vol. 9, no. 1, pp. 63-72.
Braun W, Kallen J, Mikol V, Walkinshaw MD, Wüthrich K. Three-dimensional structure actions of immunosuppressants and their immunophilins. FASEB Journal. 1995;9(1):63-72.
Braun, Werner ; Kallen, Joerg ; Mikol, Vincent ; Walkinshaw, Malcolm D. ; Wüthrich, Kurt. / Three-dimensional structure actions of immunosuppressants and their immunophilins. In: FASEB Journal. 1995 ; Vol. 9, No. 1. pp. 63-72.
@article{905b9751b7024a5d9c80261e2da1bf45,
title = "Three-dimensional structure actions of immunosuppressants and their immunophilins",
abstract = "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-FK.506-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.",
keywords = "Cyclophilin, Cyclosporin A, FK506, FKBP, Rapamycin",
author = "Werner Braun and Joerg Kallen and Vincent Mikol and Walkinshaw, {Malcolm D.} and Kurt W{\"u}thrich",
year = "1995",
language = "English (US)",
volume = "9",
pages = "63--72",
journal = "FASEB Journal",
issn = "0892-6638",
publisher = "FASEB",
number = "1",

}

TY - JOUR

T1 - Three-dimensional structure actions of immunosuppressants and their immunophilins

AU - Braun, Werner

AU - Kallen, Joerg

AU - Mikol, Vincent

AU - Walkinshaw, Malcolm D.

AU - Wüthrich, Kurt

PY - 1995

Y1 - 1995

N2 - 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-FK.506-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.

AB - 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-FK.506-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.

KW - Cyclophilin

KW - Cyclosporin A

KW - FK506

KW - FKBP

KW - Rapamycin

UR - http://www.scopus.com/inward/record.url?scp=0028852791&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028852791&partnerID=8YFLogxK

M3 - Article

VL - 9

SP - 63

EP - 72

JO - FASEB Journal

JF - FASEB Journal

SN - 0892-6638

IS - 1

ER -