%0 Journal Article %1 VanDuyne1993FKBP12FK506RapamycinStructures %A Duyne, Gregory D. Van %A Standaert, Robert F. %A Karplus, P.Andrew %A Schreiber, Stuart L. %A Clardy, Jon %D 1993 %J Journal of Molecular Biology %K FK506 FKBP Rapamycin crystal-strucutre ligand-binding tacrolimus %N 1 %P 105 - 124 %R http://dx.doi.org/10.1006/jmbi.1993.1012 %T Atomic Structures of the Human Immunophilin FKBP-12 Complexes with FK506 and Rapamycin %U http://www.sciencedirect.com/science/article/pii/S0022283683710120 %V 229 %X High resolution structures for the complexes formed by the immunosuppressive agents \FK506\ and rapamycin with the human immunophilin FKBP-12 have been determined by X-ray diffraction. FKBP-12 has a novel fold comprised of a five-stranded β-sheet wrapping around a short α-helix with an overall conical shape. Both \FK506\ and rapamycin bind in the cavity defined by the β-sheet, α-helix and three loops. Both \FK506\ and rapamycin bind in similar fashions with a set of hydrogen bonds and an unusual carbonyl binding pocket. Bound \FK506\ has different conformation than free (crystalline) \FK506\ while rapamycin's bound conformation is virtually identical to that of unbound rapamycin. FKBP-12 is a peptidyl-prolyl isomerase (PPIase), and the structures of the complexes suggest ways in which this catalytic activity could operate. The different complexes are active in suppressing different steps of T cell activation, an activity seemingly unconnected with the \PPIase\ activity.

@article{VanDuyne1993FKBP12FK506RapamycinStructures, abstract = {High resolution structures for the complexes formed by the immunosuppressive agents \{FK506\} and rapamycin with the human immunophilin FKBP-12 have been determined by X-ray diffraction. FKBP-12 has a novel fold comprised of a five-stranded β-sheet wrapping around a short α-helix with an overall conical shape. Both \{FK506\} and rapamycin bind in the cavity defined by the β-sheet, α-helix and three loops. Both \{FK506\} and rapamycin bind in similar fashions with a set of hydrogen bonds and an unusual carbonyl binding pocket. Bound \{FK506\} has different conformation than free (crystalline) \{FK506\} while rapamycin's bound conformation is virtually identical to that of unbound rapamycin. FKBP-12 is a peptidyl-prolyl isomerase (PPIase), and the structures of the complexes suggest ways in which this catalytic activity could operate. The different complexes are active in suppressing different steps of T cell activation, an activity seemingly unconnected with the \{PPIase\} activity. }, added-at = {2016-03-07T23:23:18.000+0100}, author = {Duyne, Gregory D. Van and Standaert, Robert F. and Karplus, P.Andrew and Schreiber, Stuart L. and Clardy, Jon}, biburl = {https://www.bibsonomy.org/bibtex/2ee9d5fac9815a1eedaac9b0ee45c680f/salotz}, description = {Atomic Structures of the Human Immunophilin FKBP-12 Complexes with FK506 and Rapamycin}, doi = {http://dx.doi.org/10.1006/jmbi.1993.1012}, interhash = {f48de12e69fd4fda2aa8e6dbf890a7ca}, intrahash = {ee9d5fac9815a1eedaac9b0ee45c680f}, issn = {0022-2836}, journal = {Journal of Molecular Biology }, keywords = {FK506 FKBP Rapamycin crystal-strucutre ligand-binding tacrolimus}, number = 1, pages = {105 - 124}, timestamp = {2016-03-07T23:23:18.000+0100}, title = {Atomic Structures of the Human Immunophilin FKBP-12 Complexes with FK506 and Rapamycin }, url = {http://www.sciencedirect.com/science/article/pii/S0022283683710120}, volume = 229, year = 1993 }