Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Science 10 May 1991:
Vol. 252. no. 5007, pp. 839 - 842
DOI: 10.1126/science.1709302
Prev | Table of Contents | Next

Articles

Science, Vol 252, Issue 5007, 839-842
Copyright © 1991 by American Association for the Advancement of Science

articles

Atomic structure of FKBP-FK506, an immunophilin-immunosuppressant complex

GD Van Duyne, RF Standaert, PA Karplus, SL Schreiber, and J Clardy

Department of Chemistry, Baker Laboratory, Cornell University, Ithaca, NY 14853-1301.

The structure of the human FK506 binding protein (FKBP), complexed with the immunosuppressant FK506, has been determined to 1.7 angstroms resolution by x-ray crystallography. The conformation of the protein changes little upon complexation, but the conformation of FK506 is markedly different in the bound and unbound forms. The drug's association with the protein involves five hydrogen bonds, a hydrophobic binding pocket lined with conserved aromatic residues, and an unusual carbonyl binding pocket. The nature of this complex has implications for the mechanism of rotamase catalysis and for the biological actions of FK506 and rapamycin.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
FK506-binding protein (FKBP) partitions a modified HIV protease inhibitor into blood cells and prolongs its lifetime in vivo.
P. S. Marinec, L. Chen, K. J. Barr, M. W. Mutz, G. R. Crabtree, and J. E. Gestwicki (2009)
PNAS 106, 1336-1341
   Abstract »    Full Text »    PDF »
Affinity Maturation of Tacrolimus Antibody for Improved Immunoassay Performance.
R. W. Siegel, W. Baugher, T. Rahn, S. Drengler, and J. Tyner (2008)
Clin. Chem. 54, 1008-1017
   Abstract »    Full Text »    PDF »
Noncatalytic Role of the FKBP52 Peptidyl-Prolyl Isomerase Domain in the Regulation of Steroid Hormone Signaling.
D. L. Riggs, M. B. Cox, H. L. Tardif, M. Hessling, J. Buchner, and D. F. Smith (2007)
Mol. Cell. Biol. 27, 8658-8669
   Abstract »    Full Text »    PDF »
Comparative proteomic analysis on human L-02 liver cells treated with varying concentrations of trichloroethylene.
Jianjun Liu, H. Huang, X. Xing, R. Xi, Z. Zhuang, J. Yuan, F. Yang, and J. Zhao (2007)
Toxicology and Industrial Health 23, 91-101
   Abstract »    PDF »
Organization of the biosynthetic gene cluster in Streptomyces sp. DSM 4137 for the novel neuroprotectant polyketide meridamycin.
Y. Sun, H. Hong, M. Samborskyy, T. Mironenko, P. F. Leadlay, and S. F. Haydock (2006)
Microbiology 152, 3507-3515
   Abstract »    Full Text »    PDF »
Crystal Structure and Nonhomologous End-joining Function of the Ligase Component of Mycobacterium DNA Ligase D.
D. Akey, A. Martins, J. Aniukwu, M. S. Glickman, S. Shuman, and J. M. Berger (2006)
J. Biol. Chem. 281, 13412-13423
   Abstract »    Full Text »    PDF »
Arabidopsis TARGET OF RAPAMYCIN Interacts with RAPTOR, Which Regulates the Activity of S6 Kinase in Response to Osmotic Stress Signals.
M. M. Mahfouz, S. Kim, A. J. Delauney, and D. P. S. Verma (2006)
PLANT CELL 18, 477-490
   Abstract »    Full Text »    PDF »
The Streptococcal Lipoprotein Rotamase A (SlrA) Is a Functional Peptidyl-prolyl Isomerase Involved in Pneumococcal Colonization.
P. W. M. Hermans, P. V. Adrian, C. Albert, S. Estevao, T. Hoogenboezem, I. H. T. Luijendijk, T. Kamphausen, and S. Hammerschmidt (2006)
J. Biol. Chem. 281, 968-976
   Abstract »    Full Text »    PDF »
The crystal structure of ribosomal chaperone trigger factor from Vibrio cholerae.
A. V. Ludlam, B. A. Moore, and Z. Xu (2004)
PNAS 101, 13436-13441
   Abstract »    Full Text »    PDF »
Structure of the periplasmic component of a bacterial drug efflux pump.
M. K. Higgins, E. Bokma, E. Koronakis, C. Hughes, and V. Koronakis (2004)
PNAS 101, 9994-9999
   Abstract »    Full Text »    PDF »
3D structure of human FK506-binding protein 52: Implications for the assembly of the glucocorticoid receptor/Hsp90/immunophilin heterocomplex.
B. Wu, P. Li, Y. Liu, Z. Lou, Y. Ding, C. Shu, S. Ye, M. Bartlam, B. Shen, and Z. Rao (2004)
PNAS 101, 8348-8353
   Abstract »    Full Text »    PDF »
Immunophilins and Parvulins. Superfamily of Peptidyl Prolyl Isomerases in Arabidopsis.
Z. He, L. Li, and S. Luan (2004)
Plant Physiology 134, 1248-1267
   Abstract »    Full Text »    PDF »
TWISTED DWARF1, a Unique Plasma Membrane-anchored Immunophilin-like Protein, Interacts with Arabidopsis Multidrug Resistance-like Transporters AtPGP1 and AtPGP19.
M. Geisler, H. U. Kolukisaoglu, R. Bouchard, K. Billion, J. Berger, B. Saal, N. Frangne, Z. Koncz-Kalman, C. Koncz, R. Dudler, et al. (2003)
Mol. Biol. Cell 14, 4238-4249
   Abstract »    Full Text »    PDF »
Trigger Factor-Mediated Prolyl Isomerization Influences Maturation of the Streptococcus pyogenes Cysteine Protease.
W. R. Lyon and M. G. Caparon (2003)
J. Bacteriol. 185, 3661-3667
   Abstract »    Full Text »    PDF »
Structure of the large FK506-binding protein FKBP51, an Hsp90-binding protein and a component of steroid receptor complexes.
C. R. Sinars, J. Cheung-Flynn, R. A. Rimerman, J. G. Scammell, D. F. Smith, and J. Clardy (2003)
PNAS 100, 868-873
   Abstract »    Full Text »    PDF »
High-Throughput Fluorescence Polarization Method for Identification of FKBP12 Ligands.
S. Bollini, J. J. Herbst, G. T. Gaughan, T. A. Verdoorn, J. Ditta, G. M. Dubowchik, and A. Vinitsky (2002)
J Biomol Screen 7, 526-530
   Abstract »    PDF »
Regulation of Drosophila TRPL Channels by Immunophilin FKBP59.
M. Goel, R. Garcia, M. Estacion, and W. P. Schilling (2001)
J. Biol. Chem. 276, 38762-38773
   Abstract »    Full Text »    PDF »
Experimental evidence for the correlation of bond distances in peptide groups detected in ultrahigh-resolution protein structures.
L. Esposito, L. Vitagliano, A. Zagari, and L. Mazzarella (2000)
Protein Eng. Des. Sel. 13, 825-828
   Abstract »    Full Text »    PDF »
An Inositolphosphate-Binding Immunophilin, IPBP12.
E. B. Cunningham (1999)
Blood 94, 2778-2789
   Abstract »    Full Text »    PDF »
Rapamycin Antifungal Action Is Mediated via Conserved Complexes with FKBP12 and TOR Kinase Homologs in Cryptococcus neoformans.
M. C. Cruz, L. M. Cavallo, J. M. Gorlach, G. Cox, J. R. Perfect, M. E. Cardenas, and J. Heitman (1999)
Mol. Cell. Biol. 19, 4101-4112
   Abstract »    Full Text »    PDF »
Three Amino Acid Residues Determine Selective Binding of FK506-binding Protein 12.6 to the Cardiac Ryanodine Receptor.
H.-B. Xin, K. Rogers, Y. Qi, T. Kanematsu, and S. Fleischer (1999)
J. Biol. Chem. 274, 15315-15319
   Abstract »    Full Text »    PDF »
Borrowing to make ends meet.
J. Clardy (1999)
PNAS 96, 1826-1827
   Full Text »    PDF »
Affinity modulation of small-molecule ligands by borrowing endogenous protein surfaces.
R. Briesewitz, G. T. Ray, T. J. Wandless, and G. R. Crabtree (1999)
PNAS 96, 1953-1958
   Abstract »    Full Text »    PDF »
The Wheat Peptidyl Prolyl cis-trans-Isomerase FKBP77 Is Heat Induced and Developmentally Regulated.
I. Kurek, K. Aviezer, N. Erel, E. Herman, and A. Breiman (1999)
Plant Physiology 119, 693-704
   Abstract »    Full Text »
Antibody catalysis of peptidyl-prolyl cis-trans isomerization in the folding of RNase T1.
L. Ma, L. C. Hsieh-Wilson, and P. G. Schultz (1998)
PNAS 95, 7251-7256
   Abstract »    Full Text »    PDF »
Analysis of FKBP51/FKBP52 Chimeras and Mutants for Hsp90 Binding and Association with Progesterone Receptor Complexes.
R. L. Barent, S. C. Nair, D. C. Carr, Y. Ruan, R. A. Rimerman, J. Fulton, Y. Zhang, and D. F. Smith (1998)
Mol. Endocrinol. 12, 342-354
   Abstract »    Full Text »
Functions of FKBP12 and Mitochondrial Cyclophilin Active Site Residues In Vitro and In Vivo in Saccharomyces cerevisiae.
K. Dolinski, C. Scholz, R. S. Muir, S. Rospert, F. X. Schmid, M. E. Cardenas, and J. Heitman (1997)
Mol. Biol. Cell 8, 2267-2280
   Abstract »    Full Text »
Protein Phosphatase 5 Is a Major Component of Glucocorticoid Receptor·hsp90 Complexes with Properties of an FK506-binding Immunophilin.
A. M. Silverstein, M. D. Galigniana, M.-S. Chen, J. K. Owens-Grillo, M. Chinkers, and W. B. Pratt (1997)
J. Biol. Chem. 272, 16224-16230
   Abstract »    Full Text »    PDF »
The Escherichia coli SlyD Is a Metal Ion-regulated Peptidyl-prolyl cis/trans-Isomerase.
S. Hottenrott, T. Schumann, A. Pluckthun, G. Fischer, and J.-U. Rahfeld (1997)
J. Biol. Chem. 272, 15697-15701
   Abstract »    Full Text »    PDF »
Proposed Ligand Binding Site of the Transmembrane Receptor for Neurotensin(8-13).
Y.-P. Pang, B. Cusack, K. Groshan, and E. Richelson (1996)
J. Biol. Chem. 271, 15060-15068
   Abstract »    Full Text »    PDF »
Mammalian RAFT1 kinase domain provides rapamycin-sensitive TOR function in yeast..
C M Alarcon, M E Cardenas, and J Heitman (1996)
Genes & Dev. 10, 279-288
   Abstract »    PDF »
Molecular Cloning, DNA Sequence Analysis, and Biochemical Characterization of a Novel 65-kDa FK506-binding Protein (FKBP65).
M. C. Coss, D. Winterstein, R. C. Sowder II, and S. L. Simek (1995)
J. Biol. Chem. 270, 29336-29341
   Abstract »    Full Text »    PDF »
TOR Mutations Confer Rapamycin Resistance by Preventing Interaction with FKBP12-Rapamycin.
M. C. Lorenz and J. Heitman (1995)
J. Biol. Chem. 270, 27531-27537
   Abstract »    Full Text »    PDF »
A Novel FK506 Binding Protein Can Mediate the Immunosuppressive Effects of FK506 and Is Associated with the Cardiac Ryanodine Receptor.
E. Lam, M. M. Martin, A. P. Timerman, C. Sabers, S. Fleischer, T. Lukas, R. T. Abraham, S. J. O'Keefe, E. A. O'Neill, and G. J. Wiederrecht (1995)
J. Biol. Chem. 270, 26511-26522
   Abstract »    Full Text »    PDF »
FK506 Binding Protein Mutational Analysis.
O. Futer, M. T. DeCenzo, R. A. Aldape, and D. J. Livingston (1995)
J. Biol. Chem. 270, 18935-18940
   Abstract »    Full Text »    PDF »
Solution Structure of Taxol Determined Using a Novel Feedback-Scaling Procedure for Noe-Restrained Molecular Dynamics.
R. E. Cachau, R. Gussio, J. A. Beutler, G. N. Chmurny, B. D. Hilton, G. M. Muschik, and J. W. Erickson (1994)
International Journal of High Performance Computing Applications 8, 24-34
   Abstract »    PDF »
Controlling signal transduction with synthetic ligands.
D. Spencer, T. Wandless, S. Schreiber, and G. Crabtree (1993)
Science 262, 1019-1024
   Abstract »    PDF »
Three-dimensional structure of an angiotensin II-Fab complex at 3 A: hormone recognition by an anti-idiotypic antibody.
K. Garcia, P. Ronco, P. Verroust, A. Brunger, and L. Amzel (1992)
Science 257, 502-507
   Abstract »    PDF »
A conformation of cyclosporin A in aqueous environment revealed by the X-ray structure of a cyclosporin-Fab complex.
D Altschuh, O Vix, B Rees, and J. Thierry (1992)
Science 256, 92-94
   Abstract »    PDF »
Receptor-induced conformation change of the immunosuppressant cyclosporin A.
K Wuthrich, B von Freyberg, C Weber, G Wider, R Traber, H Widmer, and W Braun (1991)
Science 254, 953-954
   PDF »
Rusting of the lock and key model for protein-ligand binding.
W. Jorgensen (1991)
Science 254, 954-955
   PDF »
Solution structure of FKBP, a rotamase enzyme and receptor for FK506 and rapamycin.
S. Michnick, M. Rosen, T. Wandless, M Karplus, and S. Schreiber (1991)
Science 252, 836-839
   Abstract »    PDF »
A CDC6 Protein-binding Peptide Selected Using a Bacterial Two-hybrid-like System Is a Cell Cycle Inhibitor.
W. Zhu, R. S. Williams, and T. Kodadek (2000)
J. Biol. Chem. 275, 32098-32105
   Abstract »    Full Text »    PDF »
A ligand-reversible dimerization system for controlling protein-protein interactions.
C. T. Rollins, V. M. Rivera, D. N. Woolfson, T. Keenan, M. Hatada, S. E. Adams, L. J. Andrade, D. Yaeger, M. R. van Schravendijk, D. A. Holt, et al. (2000)
PNAS 97, 7096-7101
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)