1FKK

ATOMIC STRUCTURE OF FKBP12, AN IMMUNOPHILIN BINDING PROTEIN

1FKK の概要

• エントリーDOI: 10.2210/pdb1fkk/pdb
• 分子名称: FK506 BINDING PROTEIN, SULFATE ION (3 entities in total)
• 機能のキーワード: fk506 binding protein, fkbp12, cis-trans prolyl-isomerase, rotamase
• 由来する生物種: Bos taurus (cattle)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 11890.49

構造登録者

Wilson, K.P.,Sintchak, M.D.,Thomson, J.A.,Navia, M.A. (登録日: 1995-08-18, 公開日: 1995-12-07, 最終更新日: 2024-02-07)

主引用文献

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

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: 15299838
DOI: 10.1107/S0907444994014514

実験手法

X-RAY DIFFRACTION (2.2 Å)