The protein cyclophilin is the major intracellular receptor for the immunosuppressive drug cyclosporin A. Cyclosporin A acts as an inhibitor of T-cell activation and can prevent graft rejection in organ and bone marrow transplantation. Cyclophilin may be responsible for mediating this immunosuppressive response. Cyclophilin also catalyses the interconversion of the cis and trans isomers of the peptidyl-prolyl amide bonds of peptide and protein substrates. Here we report the X-ray crystal structure of human recombinant cyclophilin complexed with a tetrapeptide and the identification, by nuclear magnetic resonance spectroscopy, of the specific binding site for cyclosporin A. Cyclophilin has an eight-stranded antiparallel beta-barrel structure. The prolyl isomerase substrate-binding site is coincident with the cyclosporine-binding site. These results may help to provide a structural basis for rationalizing the immunosuppressive function of the cyclosporin-cyclophilin system and will also be important in the design of improved immunosuppressant drugs.
[NMR paper] Location of the Zn(2+)-binding site on S100B as determined by NMR spectroscopy and si
Location of the Zn(2+)-binding site on S100B as determined by NMR spectroscopy and site-directed mutagenesis.
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Biochemistry. 2003 Nov 25;42(46):13410-21
Authors: Wilder PT, Baldisseri DM, Udan R, Vallely KM, Weber DJ
In addition to binding Ca(2+), the S100 protein S100B binds Zn(2+) with relatively high affinity as confirmed using isothermal titration calorimetry (ITC; K(d) = 94 +/- 17 nM). The Zn(2+)-binding site on...
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[NMR paper] A model of reversible inhibitors in the gastric H+/K+-ATPase binding site determined
A model of reversible inhibitors in the gastric H+/K+-ATPase binding site determined by rotational echo double resonance NMR.
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J Biol Chem. 2001 Nov 16;276(46):43197-204
Authors: Watts JA, Watts A, Middleton DA
Several close analogues of the noncovalent H(+)/K(+)-ATPase inhibitor SCH28080 (2-methyl-3-cyanomethyl-8-(phenylmethoxy)imidazopyridine) have been screened for activity and examined in the...
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[NMR paper] The structure of the human retinoic acid receptor-beta DNA-binding domain determined
The structure of the human retinoic acid receptor-beta DNA-binding domain determined by NMR.
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Nucleic Acids Symp Ser. 1992;(27):65-6
Authors: Katahira M, Knegtel R, Schilthius J, Boelens R, Eib D, van der Saag P, Kaptein R
The solution structure of the DNA-binding domain (DBD) of the human retinoic acid receptor-beta (hRAR-beta) has been determined by nuclear magnetic resonance (NMR) spectroscopy and distance geometry (DG). The...
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[NMR paper] Structure of human cyclophilin and its binding site for cyclosporin A determined by X
Structure of human cyclophilin and its binding site for cyclosporin A determined by X-ray crystallography and NMR spectroscopy.
http://www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--www.nature.com-images-lo_nature.gif Related Articles Structure of human cyclophilin and its binding site for cyclosporin A determined by X-ray crystallography and NMR spectroscopy.
Nature. 1991 Sep 19;353(6341):276-9
Authors: Kallen J, Spitzfaden C, Zurini MG, Wider G, Widmer H, Wüthrich K, Walkinshaw MD
The protein cyclophilin is the major intracellular...
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[NMR paper] NMR studies of [U-13C]cyclosporin A bound to cyclophilin: bound conformation and port
NMR studies of cyclosporin A bound to cyclophilin: bound conformation and portions of cyclosporin involved in binding.
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Biochemistry. 1991 Jul 2;30(26):6574-83
Authors: Fesik SW, Gampe RT, Eaton HL, Gemmecker G, Olejniczak ET, Neri P, Holzman TF, Egan DA, Edalji R, Simmer R
Cyclosporin A (CsA), a potent immunosuppressant, is known to bind with high specificity to cyclophilin (CyP), a 17.7 kDa protein with...
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[NMR paper] The NMR structure of cyclosporin A bound to cyclophilin in aqueous solution.
The NMR structure of cyclosporin A bound to cyclophilin in aqueous solution.
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Biochemistry. 1991 Jul 2;30(26):6563-74
Authors: Weber C, Wider G, von Freyberg B, Traber R, Braun W, Widmer H, Wüthrich K
Cyclosporin A bound to the presumed receptor protein cyclophilin was studied in aqueous solution at pH 6.0 by nuclear magnetic resonance spectroscopy using uniform 15N- or 13C-labeling of cyclosporin A and heteronuclear spectral editing techniques....
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[NMR paper] NMR studies of [U-13C]cyclosporin A bound to cyclophilin: bound conformation and port
NMR studies of cyclosporin A bound to cyclophilin: bound conformation and portions of cyclosporin involved in binding.
Related Articles NMR studies of cyclosporin A bound to cyclophilin: bound conformation and portions of cyclosporin involved in binding.
Biochemistry. 1991 Jul 2;30(26):6574-83
Authors: Fesik SW, Gampe RT, Eaton HL, Gemmecker G, Olejniczak ET, Neri P, Holzman TF, Egan DA, Edalji R, Simmer R
Cyclosporin A (CsA), a potent immunosuppressant, is known to bind with high specificity to cyclophilin (CyP), a 17.7 kDa protein with...
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08-21-2010 11:12 PM
[NMR paper] The NMR structure of cyclosporin A bound to cyclophilin in aqueous solution.
The NMR structure of cyclosporin A bound to cyclophilin in aqueous solution.
Related Articles The NMR structure of cyclosporin A bound to cyclophilin in aqueous solution.
Biochemistry. 1991 Jul 2;30(26):6563-74
Authors: Weber C, Wider G, von Freyberg B, Traber R, Braun W, Widmer H, Wüthrich K
Cyclosporin A bound to the presumed receptor protein cyclophilin was studied in aqueous solution at pH 6.0 by nuclear magnetic resonance spectroscopy using uniform 15N- or 13C-labeling of cyclosporin A and heteronuclear spectral editing techniques....
Structure of human cyclophilin and its binding site for cyclosporin A determined by X
Linear Mode
