PDBsum entry 1fkd

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Cis-trans isomerase PDB id
Protein chain
107 a.a. *
Waters ×64
* Residue conservation analysis
PDB id:
Name: Cis-trans isomerase
Title: Fk-506 binding protein: three-dimensional structure of thE C with the antagonist l-685,818
Structure: Fk506 binding protein. Chain: a. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606
Biol. unit: Dimer (from PQS)
1.72Å     R-factor:   0.181    
Authors: J.W.Becker,J.Rotonda,B.M.Mckeever
Key ref: J.W.Becker et al. (1993). FK-506-binding protein: three-dimensional structure of the complex with the antagonist L-685,818. J Biol Chem, 268, 11335-11339. PubMed id: 7684380
02-Dec-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   10 terms 
  Biological process     chaperone-mediated protein folding   33 terms 
  Biochemical function     ion channel binding     16 terms  


    Added reference    
J Biol Chem 268:11335-11339 (1993)
PubMed id: 7684380  
FK-506-binding protein: three-dimensional structure of the complex with the antagonist L-685,818.
J.W.Becker, J.Rotonda, B.M.McKeever, H.K.Chan, A.I.Marcy, G.Wiederrecht, J.D.Hermes, J.P.Springer.
L-685,818 differs only slightly in structure from the immunosuppressive drug FK-506, and both compounds bind with comparable affinity to the 12-kDa FK-506-binding protein (FKBP12), the major intracellular receptor for the drug. Despite these similarities, L-685,818 is a potent antagonist of both the immunosuppressive and toxic effects of the drug. Here, we present a structural analysis of this problem. Although FK-506 and L-685,818 differ greatly in pharmacology, we have found that the three-dimensional structures of their complexes with FKBP12 are essentially identical. Approximately half of each ligand is in contact with the receptor protein, and half is exposed to solvent; the exposed region includes the two sites where the compounds differ. These results indicate that the profound differences in the pharmacology of these two compounds are not caused by any difference in their interaction with FKBP12. Rather, these effects arise because relatively minor changes in the exposed part of a bound ligand have a strong effect on how FKBP12-ligand complexes interact with calcineurin, their putative intracellular target. In addition, FK-506 complexes with FKBP12 proteins from several species all inhibit mammalian calcineurin. Analysis of the three-dimensional structure of the complex with respect to residues conserved among these proteins suggests a small number of surface residues near the bound ligands that may play a critical role in interactions between the protein-drug complex and calcineurin.

Literature references that cite this PDB file's key reference

  PubMed id Reference
17387719 I.Nakanishi, D.G.Fedorov, and K.Kitaura (2007).
Molecular recognition mechanism of FK506 binding protein: an all-electron fragment molecular orbital study.
  Proteins, 68, 145-158.  
17029235 G.Gopalan, Z.He, K.P.Battaile, S.Luan, and K.Swaminathan (2006).
Structural comparison of oxidized and reduced FKBP13 from Arabidopsis thaliana.
  Proteins, 65, 789-795.  
15647740 T.Shimizu, H.Imai, K.Seki, S.Tomizawa, M.Nakamura, F.Honda, N.Kawahara, and N.Saito (2005).
Cyclophilin C-associated protein and cyclophilin C mRNA are upregulated in penumbral neurons and microglia after focal cerebral ischemia.
  J Cereb Blood Flow Metab, 25, 325-337.  
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.  
14581219 F.Sun, P.Li, Y.Ding, L.Wang, M.Bartlam, C.Shu, B.Shen, H.Jiang, S.Li, and Z.Rao (2003).
Design and structure-based study of new potential FKBP12 inhibitors.
  Biophys J, 85, 3194-3201.
PDB codes: 1j4h 1j4i
11705966 G.D.Pullinger, R.Sowdhamini, and A.J.Lax (2001).
Localization of functional domains of the mitogenic toxin of Pasteurella multocida.
  Infect Immun, 69, 7839-7850.  
11456311 X.Guo, J.F.Dillman, V.L.Dawson, and T.M.Dawson (2001).
Neuroimmunophilins: novel neuroprotective and neuroregenerative targets.
  Ann Neurol, 50, 6.  
11359520 X.Guo, V.L.Dawson, and T.M.Dawson (2001).
Neuroimmunophilin ligands exert neuroregeneration and neuroprotection in midbrain dopaminergic neurons.
  Eur J Neurosci, 13, 1683-1693.  
  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.  
8994877 B.L.Stoddard, and K.E.Flick (1996).
Calcineurin-immunosuppressor complexes.
  Curr Opin Struct Biol, 6, 770-775.  
8994885 M.A.Navia (1996).
Protein-drug complexes important for immunoregulation and organ transplantation.
  Curr Opin Struct Biol, 6, 838-847.  
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.  
8623162 S.Koprak, A.Sirotina, H.Ok, and F.J.Dumont (1996).
Depletion of the mature CD4+8- thymocyte subset by FK506 analogs correlates with their immunosuppressive and calcineurin inhibitory activities.
  Transplantation, 61, 926-932.  
  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.  
7529414 J.Clardy (1995).
The chemistry of signal transduction.
  Proc Natl Acad Sci U S A, 92, 56-61.  
  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.  
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.