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PDBsum entry 1qpl

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protein ligands Protein-protein interface(s) links
Isomerase PDB id
1qpl
Jmol
Contents
Protein chains
107 a.a. *
Ligands
587 ×2
Waters ×14
* Residue conservation analysis
PDB id:
1qpl
Name: Isomerase
Title: Fk506 binding protein (12 kda, human) complex with l-707,587
Structure: Protein (fk506-binding protein). Chain: a, c. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562
Resolution:
2.90Å     R-factor:   0.223     R-free:   0.342
Authors: J.W.Becker,J.Rotonda
Key ref: J.W.Becker et al. (1999). 32-Indolyl ether derivatives of ascomycin: three-dimensional structures of complexes with FK506-binding protein. J Med Chem, 42, 2798-2804. PubMed id: 10425089 DOI: 10.1021/jm9806042
Date:
25-May-99     Release date:   16-Aug-99    
PROCHECK
Go to PROCHECK summary
 Headers
 References

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

 Enzyme reactions 
   Enzyme class: E.C.5.2.1.8  - 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   7 terms 
  Biological process     regulation of immune response   24 terms 
  Biochemical function     ion channel binding     14 terms  

 

 
    Added reference    
 
 
DOI no: 10.1021/jm9806042 J Med Chem 42:2798-2804 (1999)
PubMed id: 10425089  
 
 
32-Indolyl ether derivatives of ascomycin: three-dimensional structures of complexes with FK506-binding protein.
J.W.Becker, J.Rotonda, J.G.Cryan, M.Martin, W.H.Parsons, P.J.Sinclair, G.Wiederrecht, F.Wong.
 
  ABSTRACT  
 
32-Indole ether derivatives of tacrolimus and ascomycin retain the potent immunosuppressive activity of their parent compounds but display reduced toxicity. In addition, their complexes with the 12-kDa FK506-binding protein (FKBP) form more stable complexes with the protein phosphatase calcineurin, the molecular target of these drugs. We have solved the three-dimensional structures of the FKBP complexes with two 32-indolyl derivatives of ascomycin. The structures of the protein and the macrolide are remarkably similar to those seen in the complexes with tacrolimus and ascomycin. The indole groups project away from the body of the complex, and multiple conformations are observed for the linkage to these groups as well as for a nearby peptide suggesting apparent flexibility in these parts of the structure. Comparison of these structures with that of the ternary complex of calcineurin, FKBP, and tacrolimus suggests that the indole groups interact with a binding site comprising elements of both the calcineurin alpha- and beta-chains and that this interaction is responsible for the increased stability of these complexes.
 

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.  
15718245 E.M.Snyder, M.Colledge, R.A.Crozier, W.S.Chen, J.D.Scott, and M.F.Bear (2005).
Role for A kinase-anchoring proteins (AKAPS) in glutamate receptor trafficking and long term synaptic depression.
  J Biol Chem, 280, 16962-16968.  
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
10951192 C.Sich, S.Improta, D.J.Cowley, C.Guenet, J.P.Merly, M.Teufel, and V.Saudek (2000).
Solution structure of a neurotrophic ligand bound to FKBP12 and its effects on protein dynamics.
  Eur J Biochem, 267, 5342-5355.
PDB code: 1f40
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.