PDBsum entry 1kt0

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Isomerase PDB id
Protein chain
357 a.a. *
SO4 ×3
Waters ×49
* Residue conservation analysis
PDB id:
Name: Isomerase
Title: Structure of the large fkbp-like protein, fkbp51, involved i receptor complexes
Structure: 51 kda fk506-binding protein. Chain: a. Synonym: fkbp51. Engineered: yes. Mutation: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: fkbp5. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693.
Biol. unit: Dimer (from PQS)
2.70Å     R-factor:   0.284     R-free:   0.375
Authors: C.R.Sinars,J.Cheung-Flynn,R.A.Rimerman,J.G.Scammell,D.F.Smit J.C.Clardy
Key ref:
C.R.Sinars et al. (2003). Structure of the large FK506-binding protein FKBP51, an Hsp90-binding protein and a component of steroid receptor complexes. Proc Natl Acad Sci U S A, 100, 868-873. PubMed id: 12538866 DOI: 10.1073/pnas.0231020100
14-Jan-02     Release date:   04-Feb-03    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
Q13451  (FKBP5_HUMAN) -  Peptidyl-prolyl cis-trans isomerase FKBP5
457 a.a.
357 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 6 residue positions (black crosses)

 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   4 terms 
  Biological process     chaperone-mediated protein folding   4 terms 
  Biochemical function     isomerase activity     4 terms  


    Added reference    
DOI no: 10.1073/pnas.0231020100 Proc Natl Acad Sci U S A 100:868-873 (2003)
PubMed id: 12538866  
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, J.Clardy.
The ability to bind immunosuppressive drugs such as cyclosporin and FK506 defines the immunophilin family of proteins, and the FK506-binding proteins form the FKBP subfamily of immunophilins. Some FKBPs, notably FKBP12 (the 12-kDa FK506-binding protein), have defined roles in regulating ion channels or cell signaling, and well established structures. Other FKBPs, especially the larger ones, participate in important biological processes, but their exact roles and the structural bases for these roles are poorly defined. FKBP51 (the 51-kDa FKBP) associates with heat shock protein 90 (Hsp90) and appears in functionally mature steroid receptor complexes. In New World monkeys, FKBP51 has been implicated in cortisol resistance. We report here the x-ray structures of human FKBP51, to 2.7 A, and squirrel monkey FKBP51, to 2.8 A, by using multiwavelength anomalous dispersion phasing. FKBP51 is composed of three domains: two consecutive FKBP domains and a three-unit repeat of the TPR (tetratricopeptide repeat) domain. This structure of a multi-FKBP domain protein clarifies the arrangement of these domains and their possible interactions with other proteins. The two FKBP domains differ by an insertion in the second that affects the formation of the progesterone receptor complex.
  Selected figure(s)  
Figure 1.
Fig. 1. Crystal structure of FKBP51. (A) The overall structure is as follows: light green is the FK1 domain, dark green is the FK2 domain, red is the TPR domain, and yellow regions are the linkers between domains. (B) In each case, coordinates of a similar domain (FKBP12, FKBP12, and the Hop TPR 2a domain) bound to a ligand [rapamycin (39), rapamycin, and Hsp90 fragment MEEVD (37), respectively] were superposed on FKBP51s domains (FK1, FK2, and TPR). The resulting ligand coordinates are shown in yellow space-filling atoms. (C) Extensive hydrogen bonding of the linker region between FK1 and FK2. The yellow bonds are the linking regions, dark-green bonds are FK2, and light-green bonds are FK1. Figs. 1-5 were rendered with MOLSCRIPT (34) and RASTER3D (35).
Figure 2.
Fig. 2. Binding pocket of FK1. FKBP12 (yellow with black labels) coordinates were superposed with FK1 of FKBP51 (green with green labels). Only one amino acid differs, at H87 FKBP51, which instead has a serine. The remaining side chains superpose well.
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21119664 L.Li, Z.Lou, and L.Wang (2011).
The role of FKBP5 in cancer aetiology and chemoresistance.
  Br J Cancer, 104, 19-23.  
20442138 D.Fusco, M.Vargiolu, M.Vidone, E.Mariani, L.F.Pennisi, E.Bonora, S.Capellari, D.Dirnberger, R.Baumeister, P.Martinelli, and G.Romeo (2010).
The RET51/FKBP52 complex and its involvement in Parkinson disease.
  Hum Mol Genet, 19, 2804-2816.  
19786507 H.E.Hassan, A.L.Myers, I.J.Lee, H.Chen, A.Coop, and N.D.Eddington (2010).
Regulation of gene expression in brain tissues of rats repeatedly treated by the highly abused opioid agonist, oxycodone: microarray profiling and gene mapping analysis.
  Drug Metab Dispos, 38, 157-167.  
20796173 H.R.Quintá, D.Maschi, C.Gomez-Sanchez, G.Piwien-Pilipuk, and M.D.Galigniana (2010).
Subcellular rearrangement of hsp90-binding immunophilins accompanies neuronal differentiation and neurite outgrowth.
  J Neurochem, 115, 716-734.  
19696786 S.Romano, A.D'Angelillo, R.Pacelli, S.Staibano, E.De Luna, R.Bisogni, E.L.Eskelinen, M.Mascolo, G.Calì, C.Arra, and M.F.Romano (2010).
Role of FK506-binding protein 51 in the control of apoptosis of irradiated melanoma cells.
  Cell Death Differ, 17, 145-157.  
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
19689428 A.J.Ramsey, L.C.Russell, and M.Chinkers (2009).
C-terminal sequences of hsp70 and hsp90 as non-specific anchors for tetratricopeptide repeat (TPR) proteins.
  Biochem J, 423, 411-419.  
19418507 C.Kozany, A.März, C.Kress, and F.Hausch (2009).
Fluorescent probes to characterise FK506-binding proteins.
  Chembiochem, 10, 1402-1410.  
19199039 E.T.Tatro, I.P.Everall, E.Masliah, B.J.Hult, G.Lucero, G.Chana, V.Soontornniyomkij, C.L.Achim, I.Grant, J.H.Atkinson, R.J.Ellis, J.A.McCutchan, T.D.Marcotte, M.Sherman, B.R.Hale, R.J.Ellis, J.A.McCutchan, S.Letendre, E.Capparelli, R.Schrier, J.Marquie-Beck, T.Alexander, J.Durelle, R.K.Heaton, M.Cherner, S.P.Woods, D.J.Moore, M.Dawson, T.Jernigan, C.Fennema-Notestine, S.L.Archibald, J.Hesselink, J.Annese, M.J.Taylor, B.Schweinsburg, E.Masliah, I.Everall, C.Achim, D.Richman, D.M.Smith, J.A.McCutchan, J.H.Atkinson, R.J.Ellis, S.Letendre, J.H.Atkinson, R.von Jaeger, A.C.Gamst, C.Cushman, D.R.Masys, I.Abramson, F.Vaida, and C.Ake (2009).
Differential expression of immunophilins FKBP51 and FKBP52 in the frontal cortex of HIV-infected patients with major depressive disorder.
  J Neuroimmune Pharmacol, 4, 218-226.  
19545546 E.T.Tatro, I.P.Everall, M.Kaul, and C.L.Achim (2009).
Modulation of glucocorticoid receptor nuclear translocation in neurons by immunophilins FKBP51 and FKBP52: implications for major depressive disorder.
  Brain Res, 1286, 1.  
18597655 E.Lin, and P.S.Chen (2008).
Pharmacogenomics with antidepressants in the STAR*D study.
  Pharmacogenomics, 9, 935-946.  
18408180 J.Hidalgo-de-Quintana, R.J.Evans, M.E.Cheetham, and J.van der Spuy (2008).
The Leber congenital amaurosis protein AIPL1 functions as part of a chaperone heterocomplex.
  Invest Ophthalmol Vis Sci, 49, 2878-2887.  
17634984 M.Palaiomylitou, A.Tartas, D.Vlachakis, D.Tzamarias, and M.Vlassi (2008).
Investigating the structural stability of the Tup1-interaction domain of Ssn6: evidence for a conformational change on the complex.
  Proteins, 70, 72-82.  
18496365 P.E.Marik, S.M.Pastores, D.Annane, G.U.Meduri, C.L.Sprung, W.Arlt, D.Keh, J.Briegel, A.Beishuizen, I.Dimopoulou, S.Tsagarakis, M.Singer, G.P.Chrousos, G.Zaloga, F.Bokhari, and M.Vogeser (2008).
Recommendations for the diagnosis and management of corticosteroid insufficiency in critically ill adult patients: consensus statements from an international task force by the American College of Critical Care Medicine.
  Crit Care Med, 36, 1937-1949.  
18412542 S.H.Millson, C.K.Vaughan, C.Zhai, M.M.Ali, B.Panaretou, P.W.Piper, L.H.Pearl, and C.Prodromou (2008).
Chaperone ligand-discrimination by the TPR-domain protein Tah1.
  Biochem J, 413, 261-268.  
18760284 V.Lamour, S.T.Rutherford, K.Kuznedelov, U.A.Ramagopal, R.L.Gourse, K.Severinov, and S.A.Darst (2008).
Crystal structure of Escherichia coli Rnk, a new RNA polymerase-interacting protein.
  J Mol Biol, 383, 367-379.
PDB code: 3bmb
18326728 X.Zhang, A.F.Clark, and T.Yorio (2008).
FK506-binding protein 51 regulates nuclear transport of the glucocorticoid receptor beta and glucocorticoid responsiveness.
  Invest Ophthalmol Vis Sci, 49, 1037-1047.  
17523132 A.Imai, H.Sahara, Y.Tamura, K.Jimbow, T.Saito, K.Ezoe, T.Yotsuyanagi, and N.Sato (2007).
Inhibition of endogenous MHC class II-restricted antigen presentation by tacrolimus (FK506) via FKBP51.
  Eur J Immunol, 37, 1730-1738.  
17938211 D.L.Riggs, M.B.Cox, H.L.Tardif, M.Hessling, J.Buchner, and D.F.Smith (2007).
Noncatalytic role of the FKBP52 peptidyl-prolyl isomerase domain in the regulation of steroid hormone signaling.
  Mol Cell Biol, 27, 8658-8669.  
17080288 K.Aviezer-Hagai, J.Skovorodnikova, M.Galigniana, O.Farchi-Pisanty, E.Maayan, S.Bocovza, Y.Efrat, P.von Koskull-Döring, N.Ohad, and A.Breiman (2007).
Arabidopsis immunophilins ROF1 (AtFKBP62) and ROF2 (AtFKBP65) exhibit tissue specificity, are heat-stress induced, and bind HSP90.
  Plant Mol Biol, 63, 237-255.  
17826298 M.Geisler, and A.Bailly (2007).
Tête-à-tête: the function of FKBPs in plant development.
  Trends Plant Sci, 12, 465-473.  
17599004 P.E.Marik (2007).
Mechanisms and clinical consequences of critical illness associated adrenal insufficiency.
  Curr Opin Crit Care, 13, 363-369.  
17142810 W.Yong, Z.Yang, S.Periyasamy, H.Chen, S.Yucel, W.Li, L.Y.Lin, I.M.Wolf, M.J.Cohn, L.S.Baskin, E.R.Sánchez, and W.Shou (2007).
Essential role for Co-chaperone Fkbp52 but not Fkbp51 in androgen receptor-mediated signaling and physiology.
  J Biol Chem, 282, 5026-5036.  
16641492 A.L.Cortajarena, and L.Regan (2006).
Ligand binding by TPR domains.
  Protein Sci, 15, 1193-1198.  
17081296 M.Gawlik, K.Moller-Ehrlich, M.Mende, M.Jovnerovski, S.Jung, B.Jabs, M.Knapp, and G.Stoeber (2006).
Is FKBP5 a genetic marker of affective psychosis? A case control study and analysis of disease related traits.
  BMC Psychiatry, 6, 52.  
16604427 M.Maestre-Martínez, F.Edlich, F.Jarczowski, M.Weiwad, G.Fischer, and C.Lücke (2006).
Solution structure of the FK506-binding domain of human FKBP38.
  J Biomol NMR, 34, 197-202.
PDB code: 2f2d
15634341 C.G.Wilson, T.Kajander, and L.Regan (2005).
The crystal structure of NlpI. A prokaryotic tetratricopeptide repeat protein with a globular fold.
  FEBS J, 272, 166-179.
PDB code: 1xnf
16193499 L.H.Li, J.M.Donald, and M.S.Golub (2005).
Review on testicular development, structure, function, and regulation in common marmoset.
  Birth Defects Res B Dev Reprod Toxicol, 74, 450-469.  
15880774 W.Wriggers, S.Chakravarty, and P.A.Jennings (2005).
Control of protein functional dynamics by peptide linkers.
  Biopolymers, 80, 736-746.  
15159550 B.Wu, P.Li, Y.Liu, Z.Lou, Y.Ding, C.Shu, S.Ye, M.Bartlam, B.Shen, and Z.Rao (2004).
3D structure of human FK506-binding protein 52: implications for the assembly of the glucocorticoid receptor/Hsp90/immunophilin heterocomplex.
  Proc Natl Acad Sci U S A, 101, 8348-8353.
PDB codes: 1p5q 1q1c 1qz2
14978266 C.Elbi, D.A.Walker, G.Romero, W.P.Sullivan, D.O.Toft, G.L.Hager, and D.B.DeFranco (2004).
Molecular chaperones function as steroid receptor nuclear mobility factors.
  Proc Natl Acad Sci U S A, 101, 2876-2881.  
15497498 D.F.Smith (2004).
Tetratricopeptide repeat cochaperones in steroid receptor complexes.
  Cell Stress Chaperones, 9, 109-121.  
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.  
12606580 D.L.Riggs, P.J.Roberts, S.C.Chirillo, J.Cheung-Flynn, V.Prapapanich, T.Ratajczak, R.Gaber, D.Picard, and D.F.Smith (2003).
The Hsp90-binding peptidylprolyl isomerase FKBP52 potentiates glucocorticoid signaling in vivo.
  EMBO J, 22, 1158-1167.  
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 codes are shown on the right.