PDBsum entry 1yat

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protein ligands links
Binding protein PDB id
Protein chain
113 a.a. *
Waters ×41
* Residue conservation analysis
PDB id:
Name: Binding protein
Title: Improved calcineurin inhibition by yeast fkbp12-drug complexes. Crystallographic and functional analysis
Structure: Fk506 binding protein. Chain: a. Engineered: yes
Source: Saccharomyces cerevisiae. Baker's yeast. Organism_taxid: 4932
2.50Å     R-factor:   0.177    
Authors: J.Rotonda,J.W.Becker
Key ref: J.Rotonda et al. (1993). Improved calcineurin inhibition by yeast FKBP12-drug complexes. Crystallographic and functional analysis. J Biol Chem, 268, 7607-7609. PubMed id: 7681823
06-Jan-93     Release date:   31-Oct-93    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P20081  (FKBP_YEAST) -  FK506-binding protein 1
114 a.a.
113 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     cytoplasm   1 term 
  Biological process     chromatin organization   4 terms 
  Biochemical function     protein binding     4 terms  


    Added reference    
J Biol Chem 268:7607-7609 (1993)
PubMed id: 7681823  
Improved calcineurin inhibition by yeast FKBP12-drug complexes. Crystallographic and functional analysis.
J.Rotonda, J.J.Burbaum, H.K.Chan, A.I.Marcy, J.W.Becker.
The protein phosphatase calcineurin is the putative target for the immunosuppressive drug FK-506. The enzyme is inhibited by the complex of the drug with its intracellular receptor, the 12-kDa FK-506-binding protein (FKBP12), and the strength of inhibition usually correlates strongly with immunosuppressive potency. We find, however, that the complex of yeast FKBP12 with L-685,818, a well characterized antagonist of FK-506 immunosuppression, is a potent inhibitor of calcineurin. The corresponding human complex does not inhibit the enzyme, and both human and yeast complexes with FK-506 do inhibit. To understand the structural basis of these findings, we have determined the three-dimensional structure of the complex of yeast FKBP12 with FK-506 by x-ray crystallography, and have found that the structure of the yeast complex is strikingly similar to its human homolog. These observations indicate that specific sequence elements in the yeast protein provide stronger binding interactions with a heterologous calcineurin than do the corresponding elements in the human protein, and suggest structural modifications that may improve the potency of this class of immunosuppressants.

Literature references that cite this PDB file's key reference

  PubMed id Reference
17505522 W.J.Steinbach, J.L.Reedy, R.A.Cramer, J.R.Perfect, and J.Heitman (2007).
Harnessing calcineurin as a novel anti-infective agent against invasive fungal infections.
  Nat Rev Microbiol, 5, 418-430.  
12604527 C.Onyewu, J.R.Blankenship, M.Del Poeta, and J.Heitman (2003).
Ergosterol biosynthesis inhibitors become fungicidal when combined with calcineurin inhibitors against Candida albicans, Candida glabrata, and Candida krusei.
  Antimicrob Agents Chemother, 47, 956-964.  
11847103 M.C.Cruz, A.L.Goldstein, J.R.Blankenship, M.Del Poeta, D.Davis, M.E.Cardenas, J.R.Perfect, J.H.McCusker, and J.Heitman (2002).
Calcineurin is essential for survival during membrane stress in Candida albicans.
  EMBO J, 21, 546-559.  
11724963 H.Patzelt, S.Rüdiger, D.Brehmer, G.Kramer, S.Vorderwülbecke, E.Schaffitzel, A.Waitz, T.Hesterkamp, L.Dong, J.Schneider-Mergener, B.Bukau, and E.Deuerling (2001).
Binding specificity of Escherichia coli trigger factor.
  Proc Natl Acad Sci U S A, 98, 14244-14249.  
10931176 A.Galat (2000).
Sequence diversification of the FK506-binding proteins in several different genomes.
  Eur J Biochem, 267, 4945-4959.  
  10049913 K.J.Dolinski, and J.Heitman (1999).
Hmo1p, a high mobility group 1/2 homolog, genetically and physically interacts with the yeast FKBP12 prolyl isomerase.
  Genetics, 151, 935-944.  
9807840 M.E.Cardenas, A.Sanfridson, N.S.Cutler, and J.Heitman (1998).
Signal-transduction cascades as targets for therapeutic intervention by natural products.
  Trends Biotechnol, 16, 427-433.  
  8980772 A.Odom, M.Del Poeta, J.Perfect, and J.Heitman (1997).
The immunosuppressant FK506 and its nonimmunosuppressive analog L-685,818 are toxic to Cryptococcus neoformans by inhibition of a common target protein.
  Antimicrob Agents Chemother, 41, 156-161.  
9184205 A.Odom, S.Muir, E.Lim, D.L.Toffaletti, J.Perfect, and J.Heitman (1997).
Calcineurin is required for virulence of Cryptococcus neoformans.
  EMBO J, 16, 2576-2589.  
  9362068 K.Dolinski, C.Scholz, R.S.Muir, S.Rospert, F.X.Schmid, M.E.Cardenas, and J.Heitman (1997).
Functions of FKBP12 and mitochondrial cyclophilin active site residues in vitro and in vivo in Saccharomyces cerevisiae.
  Mol Biol Cell, 8, 2267-2280.  
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.  
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
  7540135 A.Moro, F.Ruiz-Cabello, A.Fernández-Cano, R.P.Stock, and A.González (1995).
Secretion by Trypanosoma cruzi of a peptidyl-prolyl cis-trans isomerase involved in cell infection.
  EMBO J, 14, 2483-2490.  
  7542743 G.Baughman, G.J.Wiederrecht, N.F.Campbell, M.M.Martin, and S.Bourgeois (1995).
FKBP51, a novel T-cell-specific immunophilin capable of calcineurin inhibition.
  Mol Cell Biol, 15, 4395-4402.  
9383449 J.I.Luengo, D.S.Yamashita, D.Dunnington, A.K.Beck, L.W.Rozamus, H.K.Yen, M.J.Bossard, M.A.Levy, A.Hand, and T.Newman-Tarr (1995).
Structure-activity studies of rapamycin analogs: evidence that the C-7 methoxy group is part of the effector domain and positioned at the FKBP12-FRAP interface.
  Chem Biol, 2, 471-481.  
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.  
  8563622 S.Itoh, and M.A.Navia (1995).
Structure comparison of native and mutant human recombinant FKBP12 complexes with the immunosuppressant drug FK506 (tacrolimus).
  Protein Sci, 4, 2261-2268.  
7525596 B.M.Benton, J.H.Zang, and J.Thorner (1994).
A novel FK506- and rapamycin-binding protein (FPR3 gene product) in the yeast Saccharomyces cerevisiae is a proline rotamase localized to the nucleolus.
  J Cell Biol, 127, 623-639.  
  7529175 M.E.Cardenas, C.Hemenway, R.S.Muir, R.Ye, D.Fiorentino, and J.Heitman (1994).
Immunophilins interact with calcineurin in the absence of exogenous immunosuppressive ligands.
  EMBO J, 13, 5944-5957.  
8404888 A.Galat (1993).
Peptidylproline cis-trans-isomerases: immunophilins.
  Eur J Biochem, 216, 689-707.  
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.