PDBsum entry 1fkr

Go to PDB code: 
protein links
Cis-trans isomerase PDB id
Jmol PyMol
Protein chain
107 a.a. *
* Residue conservation analysis
PDB id:
Name: Cis-trans isomerase
Title: Solution structure of fkbp, a rotamase enzyme and receptor for fk506 and rapamycin
Structure: Fk506 and rapamycin-binding protein. Chain: a. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Cell_line: s2
NMR struc: 20 models
Authors: S.W.Michnick,M.K.Rosen,T.J.Wandless,M.Karplus,S.L.Schreiber
Key ref: S.W.Michnick et al. (1991). Solution structure of FKBP, a rotamase enzyme and receptor for FK506 and rapamycin. Science, 252, 836-839. PubMed id: 1709301 DOI: 10.1126/science.1709301
05-Mar-92     Release date:   31-Jan-94    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P62942  (FKB1A_HUMAN) -  Peptidyl-prolyl cis-trans isomerase FKBP1A
108 a.a.
107 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - Peptidylprolyl isomerase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Peptidylproline (omega=180) = peptidylproline (omega=0)
Peptidylproline (omega=180)
= peptidylproline (omega=0)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     membrane   6 terms 
  Biological process     chaperone-mediated protein folding   26 terms 
  Biochemical function     ion channel binding     12 terms  


    Added reference    
DOI no: 10.1126/science.1709301 Science 252:836-839 (1991)
PubMed id: 1709301  
Solution structure of FKBP, a rotamase enzyme and receptor for FK506 and rapamycin.
S.W.Michnick, M.K.Rosen, T.J.Wandless, M.Karplus, S.L.Schreiber.
Immunophilins, when complexed to immunosuppressive ligands, appear to inhibit signal transduction pathways that result in exocytosis and transcription. The solution structure of one of these, the human FK506 and rapamycin binding protein (FKBP), has been determined by nuclear magnetic resonance (NMR). FKBP has a previously unobserved antiparallel beta-sheet folding topology that results in a novel loop crossing and produces a large cavity lined by a conserved array of aromatic residues; this cavity serves as the rotamase active site and drug-binding pocket. There are other significant structural features (such as a protruding positively charged loop and an apparently flexible loop) that may be involved in the biological activity of FKBP.

Literature references that cite this PDB file's key reference

  PubMed id Reference
21087465 J.C.Ahn, D.W.Kim, Y.N.You, M.S.Seok, J.M.Park, H.Hwang, B.G.Kim, S.Luan, H.S.Park, and H.S.Cho (2010).
Classification of rice (Oryza sativa L. Japonica nipponbare) immunophilins (FKBPs, CYPs) and expression patterns under water stress.
  BMC Plant Biol, 10, 253.  
20552687 M.Gaudet, N.Remtulla, S.E.Jackson, E.R.Main, D.G.Bracewell, G.Aeppli, and P.A.Dalby (2010).
Protein denaturation and protein:drugs interactions from intrinsic protein fluorescence measurements at the nanolitre scale.
  Protein Sci, 19, 1544-1554.  
20572013 R.Alag, I.A.Qureshi, N.Bharatham, J.Shin, J.Lescar, and H.S.Yoon (2010).
NMR and crystallographic structures of the FK506 binding domain of human malarial parasite Plasmodium vivax FKBP35.
  Protein Sci, 19, 1577-1586.
PDB code: 3ihz
20306145 T.Unger, O.Dym, S.Albeck, Y.Jacobovitch, R.Bernehim, D.Marom, O.Pisanty, and A.Breiman (2010).
Crystal structure of the three FK506 binding protein domains of wheat FKBP73: evidence for a unique wFK73_2 domain.
  J Struct Funct Genomics, 11, 113-123.
PDB codes: 3jxv 3jym
19645725 L.Martino, Y.He, K.L.Hands-Taylor, E.R.Valentine, G.Kelly, C.Giancola, and M.R.Conte (2009).
The interaction of the Escherichia coli protein SlyD with nickel ions illuminates the mechanism of regulation of its peptidyl-prolyl isomerase activity.
  FEBS J, 276, 4529-4544.
PDB code: 2kfw
18366641 A.Ceymann, M.Horstmann, P.Ehses, K.Schweimer, A.K.Paschke, M.Steinert, and C.Faber (2008).
Solution structure of the Legionella pneumophila Mip-rapamycin complex.
  BMC Struct Biol, 8, 17.
PDB code: 2vcd
17876830 C.B.Kang, H.Ye, H.R.Yoon, and H.S.Yoon (2008).
Solution structure of FK506 binding domain (FKBD) of Plasmodium falciparum FK506 binding protein 35 (PfFKBP35).
  Proteins, 70, 300-302.
PDB code: 2ofn
18067292 J.J.Graziano, W.Liu, R.Perera, B.H.Geierstanger, S.A.Lesley, and P.G.Schultz (2008).
Selecting folded proteins from a library of secondary structural elements.
  J Am Chem Soc, 130, 176-185.  
18576636 S.E.Cellitti, D.H.Jones, L.Lagpacan, X.Hao, Q.Zhang, H.Hu, S.M.Brittain, A.Brinker, J.Caldwell, B.Bursulaya, G.Spraggon, A.Brock, Y.Ryu, T.Uno, P.G.Schultz, and B.H.Geierstanger (2008).
In vivo incorporation of unnatural amino acids to probe structure, dynamics, and ligand binding in a large protein by nuclear magnetic resonance spectroscopy.
  J Am Chem Soc, 130, 9268-9281.  
17541991 C.H.Röhrig, C.Loch, J.Y.Guan, G.Siegal, and M.Overhand (2007).
Fragment-Based Synthesis and SAR of Modified FKBP Ligands: Influence of Different Linking on Binding Affinity.
  ChemMedChem, 2, 1054-1070.  
17461729 V.Villalobos, S.Naik, and D.Piwnica-Worms (2007).
Current state of imaging protein-protein interactions in vivo with genetically encoded reporters.
  Annu Rev Biomed Eng, 9, 321-349.  
17242738 Z.Li, and T.Lazaridis (2007).
Water at biomolecular binding interfaces.
  Phys Chem Chem Phys, 9, 573-581.  
17096757 A.D.Schachter, M.R.Benfield, R.J.Wyatt, P.C.Grimm, R.S.Fennell, J.T.Herrin, D.S.Lirenman, R.A.McDonald, R.Munoz-Arizpe, and W.E.Harmon (2006).
Sirolimus pharmacokinetics in pediatric renal transplant recipients receiving calcineurin inhibitor co-therapy.
  Pediatr Transplant, 10, 914-919.  
16864577 J.J.Tate, R.Rai, and T.G.Cooper (2006).
Ammonia-specific regulation of Gln3 localization in Saccharomyces cerevisiae by protein kinase Npr1.
  J Biol Chem, 281, 28460-28469.  
16596453 S.L.Rulten, R.A.Kinloch, H.Tateossian, C.Robinson, L.Gettins, and J.E.Kay (2006).
The human FK506-binding proteins: characterization of human FKBP19.
  Mamm Genome, 17, 322-331.  
16231289 H.Li, A.D.Robertson, and J.H.Jensen (2005).
Very fast empirical prediction and rationalization of protein pKa values.
  Proteins, 61, 704-721.  
15937899 S.Park, and J.G.Saven (2005).
Statistical and molecular dynamics studies of buried waters in globular proteins.
  Proteins, 60, 450-463.  
14997571 M.Zacharias (2004).
Rapid protein-ligand docking using soft modes from molecular dynamics simulations to account for protein deformability: binding of FK506 to FKBP.
  Proteins, 54, 759-767.  
15201156 S.E.Lehnart, X.H.Wehrens, A.Kushnir, and A.R.Marks (2004).
Cardiac ryanodine receptor function and regulation in heart disease.
  Ann N Y Acad Sci, 1015, 144-159.  
14981505 T.Kuzuhara, and M.Horikoshi (2004).
A nuclear FK506-binding protein is a histone chaperone regulating rDNA silencing.
  Nat Struct Mol Biol, 11, 275-283.  
12603318 A.G.Tzakos, A.M.Bonvin, A.Troganis, P.Cordopatis, M.L.Amzel, I.P.Gerothanassis, and N.A.van Nuland (2003).
On the molecular basis of the recognition of angiotensin II (AII). NMR structure of AII in solution compared with the X-ray structure of AII bound to the mAb Fab131.
  Eur J Biochem, 270, 849-860.  
12579579 J.H.Lin, A.L.Perryman, J.R.Schames, and J.A.McCammon (2003).
The relaxed complex method: Accommodating receptor flexibility for drug design with an improved scoring scheme.
  Biopolymers, 68, 47-62.  
12052773 P.E.Shaw (2002).
Peptidyl-prolyl isomerases: a new twist to transcription.
  EMBO Rep, 3, 521-526.  
11751578 P.J.Pereira, M.C.Vega, E.González-Rey, R.Fernández-Carazo, S.Macedo-Ribeiro, F.X.Gomis-Rüth, A.González, and M.Coll (2002).
Trypanosoma cruzi macrophage infectivity potentiator has a rotamase core and a highly exposed alpha-helix.
  EMBO Rep, 3, 88-94.
PDB code: 1jvw
12410806 T.Kamphausen, J.Fanghänel, D.Neumann, B.Schulz, and J.U.Rahfeld (2002).
Characterization of Arabidopsis thaliana AtFKBP42 that is membrane-bound and interacts with Hsp90.
  Plant J, 32, 263-276.  
12045568 T.M.Myckatyn, R.A.Ellis, A.G.Grand, S.K.Sen, J.B.Lowe, D.A.Hunter, and S.E.Mackinnon (2002).
The effects of rapamycin in murine peripheral nerve isografts and allografts.
  Plast Reconstr Surg, 109, 2405-2417.  
11514681 A.Korepanova, C.Douglas, I.Leyngold, and T.M.Logan (2001).
N-terminal extension changes the folding mechanism of the FK506-binding protein.
  Protein Sci, 10, 1905-1910.  
11524681 A.Riboldi-Tunnicliffe, B.König, S.Jessen, M.S.Weiss, J.Rahfeld, J.Hacker, G.Fischer, and R.Hilgenfeld (2001).
Crystal structure of Mip, a prolylisomerase from Legionella pneumophila.
  Nat Struct Biol, 8, 779-783.
PDB code: 1fd9
11340064 L.Mirny, and E.Shakhnovich (2001).
Protein folding theory: from lattice to all-atom models.
  Annu Rev Biophys Biomol Struct, 30, 361-396.  
10784028 I.Nakanishi, A.Fujikawa, K.Imai, and A.Sato (2000).
1H-NMR determination of the solution structure and absolute configuration of FR134043, a novel inhibitor of human leukocyte elastase.
  J Pept Res, 55, 120-128.  
11058892 M.T.Ivery (2000).
Immunophilins: switched on protein binding domains?
  Med Res Rev, 20, 452-484.  
10089303 J.Liang, J.Choi, and J.Clardy (1999).
Refined structure of the FKBP12-rapamycin-FRB ternary complex at 2.2 A resolution.
  Acta Crystallogr D Biol Crystallogr, 55, 736-744.
PDB codes: 1nsg 2fap 3fap 4fap
9558354 E.R.Main, K.F.Fulton, and S.E.Jackson (1998).
Context-dependent nature of destabilizing mutations on the stability of FKBP12.
  Biochemistry, 37, 6145-6153.  
9164465 C.Brenner, P.Garrison, J.Gilmour, D.Peisach, D.Ringe, G.A.Petsko, and J.M.Lowenstein (1997).
Crystal structures of HINT demonstrate that histidine triad proteins are GalT-related nucleotide-binding proteins.
  Nat Struct Biol, 4, 231-238.
PDB codes: 3rhn 4rhn 5rhn 6rhn
9432007 F.Goossens, G.Vanhoof, I.De Meester, K.Augustyns, M.Borloo, D.Tourwe, A.Haemers, and S.Scharpé (1997).
Development and evaluation of peptide-based prolyl oligopeptidase inhibitors--introduction of N-benzyloxycarbonyl-prolyl-3-fluoropyrrolidine as a lead in inhibitor design.
  Eur J Biochem, 250, 177-183.  
  9129559 G.M.Ferron, E.V.Mishina, J.J.Zimmerman, and W.J.Jusko (1997).
Population pharmacokinetics of sirolimus in kidney transplant patients.
  Clin Pharmacol Ther, 61, 416-428.  
  9144770 K.V.Soman, B.A.Hanks, H.Tien, M.V.Chari, K.D.O'Neal, and J.D.Morrisett (1997).
Template-based docking of a prolactin receptor proline-rich motif octapeptide to FKBP12: implications for cytokine receptor signaling.
  Protein Sci, 6, 999.  
9200682 N.Rouviere, M.Vincent, C.T.Craescu, and J.Gallay (1997).
Immunosuppressor binding to the immunophilin FKBP59 affects the local structural dynamics of a surface beta-strand: time-resolved fluorescence study.
  Biochemistry, 36, 7339-7352.  
8612612 A.Galat (1996).
A note on circular-dichroic-constrained prediction of protein secondary structure.
  Eur J Biochem, 236, 428-435.  
8780506 C.T.Craescu, N.Rouvière, A.Popescu, E.Cerpolini, M.C.Lebeau, E.E.Baulieu, and J.Mispelter (1996).
Three-dimensional structure of the immunophilin-like domain of FKBP59 in solution.
  Biochemistry, 35, 11045-11052.
PDB codes: 1rot 1rou
8941644 M.Poon, S.O.Marx, R.Gallo, J.J.Badimon, M.B.Taubman, and A.R.Marks (1996).
Rapamycin inhibits vascular smooth muscle cell migration.
  J Clin Invest, 98, 2277-2283.  
8785272 N.D.Silva, and F.G.Prendergast (1996).
Tryptophan dynamics of the FK506 binding protein: time-resolved fluorescence and simulations.
  Biophys J, 70, 1122-1137.  
8633085 T.Hesterkamp, S.Hauser, H.Lütcke, and B.Bukau (1996).
Escherichia coli trigger factor is a prolyl isomerase that associates with nascent polypeptide chains.
  Proc Natl Acad Sci U S A, 93, 4437-4441.  
8914512 V.A.Vucich, and C.S.Gasser (1996).
Novel structure of a high molecular weight FK506 binding protein from Arabidopsis thaliana.
  Mol Gen Genet, 252, 510-517.  
  7591108 E.Wintermeyer, B.Ludwig, M.Steinert, B.Schmidt, G.Fischer, and J.Hacker (1995).
Influence of site specifically altered Mip proteins on intracellular survival of Legionella pneumophila in eukaryotic cells.
  Infect Immun, 63, 4576-4583.  
7529414 J.Clardy (1995).
The chemistry of signal transduction.
  Proc Natl Acad Sci U S A, 92, 56-61.  
7544285 N.Rouvière-Fourmy, C.T.Craescu, J.Mispelter, M.C.Lebeau, and E.E.Baulieu (1995).
1H and 15N assignment of NMR spectrum, secondary structure and global folding of the immunophilin-like domain of the 59-kDa FK506-binding protein.
  Eur J Biochem, 231, 761-772.  
7669348 W.D.Roof, and R.Young (1995).
Phi X174 lysis requires slyD, a host gene which is related to the FKBP family of peptidyl-prolyl cis-trans isomerases.
  FEMS Microbiol Rev, 17, 213-218.  
7516906 B.Ludwig, J.Rahfeld, B.Schmidt, K.Mann, E.Wintermeyer, G.Fischer, and J.Hacker (1994).
Characterization of Mip proteins of Legionella pneumophila.
  FEMS Microbiol Lett, 118, 23-30.  
8075536 C.Spitzfaden, W.Braun, G.Wider, H.Widmer, and K.Wüthrich (1994).
Determination of the NMR solution structure of the cyclophilin A-cyclosporin A complex.
  J Biomol NMR, 4, 463-482.
PDB code: 3cys
7510408 P.R.Connelly, R.A.Aldape, F.J.Bruzzese, S.P.Chambers, M.J.Fitzgibbon, M.A.Fleming, S.Itoh, D.J.Livingston, M.A.Navia, and J.A.Thomson (1994).
Enthalpy of hydrogen bond formation in a protein-ligand binding reaction.
  Proc Natl Acad Sci U S A, 91, 1964-1968.  
7682281 A.G.Lundemose, J.E.Kay, and J.H.Pearce (1993).
Chlamydia trachomatis Mip-like protein has peptidyl-prolyl cis/trans isomerase activity that is inhibited by FK506 and rapamycin and is implicated in initiation of chlamydial infection.
  Mol Microbiol, 7, 777-783.  
8404888 A.Galat (1993).
Peptidylproline cis-trans-isomerases: immunophilins.
  Eur J Biochem, 216, 689-707.  
7526121 J.Hacker, and G.Fischer (1993).
Immunophilins: structure-function relationship and possible role in microbial pathogenicity.
  Mol Microbiol, 10, 445-456.  
7682113 R.X.Xu, D.Nettesheim, E.T.Olejniczak, R.Meadows, G.Gemmecker, and S.W.Fesik (1993).
1H, 13C, and 15N assignments and secondary structure of the FK506 binding protein when bound to ascomycin.
  Biopolymers, 33, 535-550.  
8473916 S.H.Rotstein, and M.A.Murcko (1993).
GenStar: a method for de novo drug design.
  J Comput Aided Mol Des, 7, 23-43.  
7689377 S.W.Fesik (1993).
NMR structure-based drug design.
  J Biomol NMR, 3, 261-269.  
1563628 A.Ferrara, R.Cafferkey, and G.P.Livi (1992).
Cloning and sequence analysis of a rapamycin-binding protein-encoding gene (RBP1) from Candida albicans.
  Gene, 113, 125-127.  
1371354 B.A.Sampson, and E.C.Gotschlich (1992).
Neisseria meningitidis encodes an FK506-inhibitable rotamase.
  Proc Natl Acad Sci U S A, 89, 1164-1168.  
1375171 C.A.Lepre, J.A.Thomson, and J.M.Moore (1992).
Solution structure of FK506 bound to FKBP-12.
  FEBS Lett, 302, 89-96.  
1502562 G.Russell, R.Graveley, J.Seid,, and H.Skjodt (1992).
Mechanisms of action of cyclosporine and effects on connective tissues.
  Semin Arthritis Rheum, 21, 16-22.  
1631118 I.Callebaut, J.M.Renoir, M.C.Lebeau, N.Massol, A.Burny, E.E.Baulieu, and J.P.Mornon (1992).
An immunophilin that binds M(r) 90,000 heat shock protein: main structural features of a mammalian p59 protein.
  Proc Natl Acad Sci U S A, 89, 6270-6274.  
1279908 J.A.Partaledis, M.A.Fleming, M.W.Harding, and V.Berlin (1992).
Saccharomyces cerevisiae contains a homolog of human FKBP-13, a membrane-associated FK506/rapamycin binding protein.
  Yeast, 8, 673-680.  
1528078 M.D.Walkinshaw (1992).
Protein targets for structure-based drug design.
  Med Res Rev, 12, 317-372.  
1508047 M.Geistlich, R.Losick, J.R.Turner, and R.N.Rao (1992).
Characterization of a novel regulatory gene governing the expression of a polyketide synthase gene in Streptomyces ambofaciens.
  Mol Microbiol, 6, 2019-2029.  
1375751 P.R.Connelly, and J.A.Thomson (1992).
Heat capacity changes and hydrophobic interactions in the binding of FK506 and rapamycin to the FK506 binding protein.
  Proc Natl Acad Sci U S A, 89, 4781-4785.  
1382438 R.Edalji, T.J.Pilot-Matias, S.D.Pratt, D.A.Egan, J.M.Severin, E.G.Gubbins, A.M.Petros, S.W.Fesik, N.S.Burres, and T.F.Holzman (1992).
High-level expression of recombinant human FK-binding protein from a fusion precursor.
  J Protein Chem, 11, 213-223.  
1375189 V.A.Ruff, J.E.McGee, A.W.Yem, M.R.Deibel, and K.L.Leach (1992).
FKBP-12 is not an inhibitor of protein kinase C.
  Immunol Invest, 21, 259-273.  
1368432 W.J.Chazin (1992).
NMR structures and methodology.
  Curr Opin Biotechnol, 3, 326-332.  
1716181 F.McKeon (1991).
When worlds collide: immunosuppressants meet protein phosphatases.
  Cell, 66, 823-826.  
1946361 H.M.Ke, L.D.Zydowsky, J.Liu, and C.T.Walsh (1991).
Crystal structure of recombinant human T-cell cyclophilin A at 2.5 A resolution.
  Proc Natl Acad Sci U S A, 88, 9483-9487.  
1715244 J.Liu, J.D.Farmer, W.S.Lane, J.Friedman, I.Weissman, and S.L.Schreiber (1991).
Calcineurin is a common target of cyclophilin-cyclosporin A and FKBP-FK506 complexes.
  Cell, 66, 807-815.  
1722474 P.A.Nelson, J.A.Lippke, M.A.Murcko, S.L.Rosborough, and D.A.Peattie (1991).
cDNA encoding murine FK506-binding protein (FKBP): nucleotide and deduced amino acid sequence.
  Gene, 109, 255-258.  
1743298 P.Neri, R.Meadows, G.Gemmecker, E.Olejniczak, D.Nettesheim, T.Logan, R.Simmer, R.Helfrich, T.Holzman, and J.Severin (1991).
1H, 13C and 15N backbone assignments of cyclophilin when bound to cyclosporin A (CsA) and preliminary structural characterization of the CsA binding site.
  FEBS Lett, 294, 81-88.  
15336129 R.L.Stein (1991).
Exploring the catalytic activity of immunophilins.
  Curr Biol, 1, 234-236.  
1713687 Y.J.Jin, M.W.Albers, W.S.Lane, B.E.Bierer, S.L.Schreiber, and S.J.Burakoff (1991).
Molecular cloning of a membrane-associated human FK506- and rapamycin-binding protein, FKBP-13.
  Proc Natl Acad Sci U S A, 88, 6677-6681.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.