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Title
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X-ray structure of calcineurin inhibited by the immunophilin-immunosuppressant FKBP12-FK506 complex.
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Authors
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J.P.Griffith,
J.L.Kim,
E.E.Kim,
M.D.Sintchak,
J.A.Thomson,
M.J.Fitzgibbon,
M.A.Fleming,
P.R.Caron,
K.Hsiao,
M.A.Navia.
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Ref.
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Cell, 1995,
82,
507-522.
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PubMed id
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Abstract
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The X-ray structure of the ternary complex of a calcineurin A fragment,
calcineurin B, FKBP12, and the immunosuppressant drug FK506 (also known as
tacrolimus) has been determined at 2.5 A resolution, providing a description of
how FK506 functions at the atomic level. In the structure, the FKBP12-FK506
binary complex does not contact the phosphatase active site on calcineurin A
that is more than 10 A removed. Instead, FKBP12-FK506 is so positioned that it
can inhibit the dephosphorylation of its macromolecular substrates by physically
hindering their approach to the active site. The ternary complex described here
represents the three-dimensional structure of a Ser/Thr protein phosphatase and
provides a structural basis for understanding calcineurin inhibition by
FKBP12-FK506.
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