1FKK
ATOMIC STRUCTURE OF FKBP12, AN IMMUNOPHILIN BINDING PROTEIN
Summary for 1FKK
| Entry DOI | 10.2210/pdb1fkk/pdb |
| Descriptor | FK506 BINDING PROTEIN, SULFATE ION (3 entities in total) |
| Functional Keywords | fk506 binding protein, fkbp12, cis-trans prolyl-isomerase, rotamase |
| Biological source | Bos taurus (cattle) |
| Total number of polymer chains | 1 |
| Total formula weight | 11890.49 |
| Authors | Wilson, K.P.,Sintchak, M.D.,Thomson, J.A.,Navia, M.A. (deposition date: 1995-08-18, release date: 1995-12-07, Last modification date: 2024-02-07) |
| Primary citation | Wilson, K.P.,Yamashita, M.M.,Sintchak, M.D.,Rotstein, S.H.,Murcko, M.A.,Boger, J.,Thomson, J.A.,Fitzgibbon, M.J.,Black, J.R.,Navia, M.A. Comparative X-ray structures of the major binding protein for the immunosuppressant FK506 (tacrolimus) in unliganded form and in complex with FK506 and rapamycin. Acta Crystallogr.,Sect.D, 51:511-521, 1995 Cited by PubMed Abstract: FK506 (tacrolimus) is a natural product now approved in the US and Japan for organ transplantation. FK506, in complex with its 12 kDa cytosolic receptor (FKBP12), is a potent agonist of immunosuppression through the inhibition of the phosphatase activity of calcineurin. Rapamycin (sirolimus), which is itself an immunosuppressant by a different mechanism, completes with FK506 for binding to FKBP12 and thereby acts as an antagonist of calcineurin inhibition. We have solved the X-ray structure of unliganded FKBP12 and of FKBP12 in complex with FK506 and with rapamycin; these structures show localized differences in conformation and mobility in those regions of the protein that are known, by site-directed mutagenesis, to be involved in calcineurin inhibition. A comparison of 16 additional X-ray structures of FKBP12 in complex with FKBP12-binding ligands, where those structures were determined from different crystal forms with distinct packing arrangements, lends significance to the observed structural variability and suggests that it represents an intrinsic functional characteristic of the protein. Similar differences have been observed for FKBP12 before, but were considered artifacts of crystal-packing interactions. We suggest that immunosuppressive ligands express their differential effects in part by modulating the conformation of FKBP12, in agreement with mutagenesis experiments on the protein, and not simply through differences in the ligand structures themselves. PubMed: 15299838DOI: 10.1107/S0907444994014514 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.2 Å) |
Structure validation
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