1TCO

TERNARY COMPLEX OF A CALCINEURIN A FRAGMENT, CALCINEURIN B, FKBP12 AND THE IMMUNOSUPPRESSANT DRUG FK506 (TACROLIMUS)

Summary for 1TCO

• Entry DOI: 10.2210/pdb1tco/pdb
• Descriptor: SERINE/THREONINE PHOSPHATASE B2, FK506-BINDING PROTEIN, ZINC ION, ... (10 entities in total)
• Functional Keywords: complex (hydrolase-isomerase), immunosuppressant, complex (hydrolase-isomerase) complex, complex (hydrolase/isomerase)
• Biological source: Bos taurus (cattle); More
• Cellular location: Nucleus (By similarity): P48452; Cytoplasm: P62942
• Total number of polymer chains: 3
• Total formula weight: 75364.00

Authors

Griffith, J.P.,Kim, J.L.,Kim, E.E.,Sintchak, M.D.,Thomson, J.A.,Fitzgibbon, M.J.,Fleming, M.A.,Caron, P.R.,Hsiao, K.,Navia, M.A. (deposition date: 1996-08-21, release date: 1997-02-12, Last modification date: 2024-11-06)

Primary citation

Griffith, J.P.,Kim, J.L.,Kim, E.E.,Sintchak, M.D.,Thomson, J.A.,Fitzgibbon, M.J.,Fleming, M.A.,Caron, P.R.,Hsiao, K.,Navia, M.A.
X-ray structure of calcineurin inhibited by the immunophilin-immunosuppressant FKBP12-FK506 complex.
Cell(Cambridge,Mass.), 82:507-522, 1995

PubMed Abstract: 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.

PubMed: 7543369
DOI: 10.1016/0092-8674(95)90439-5

Experimental method

X-RAY DIFFRACTION (2.5 Å)