PDBsum entry 1cwb

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protein Protein-protein interface(s) links
Isomerase/immunosuppressant PDB id
Protein chains
165 a.a. *
11 a.a. *
Waters ×131
* Residue conservation analysis
PDB id:
Name: Isomerase/immunosuppressant
Title: The x-ray structure of (mebm2t)1-cyclosporin complexed with cyclophilin a provides an explanation for its anomalously h immunosuppressive activity
Structure: Peptidyl-prolyl cis-trans isomerase a. Chain: a. Synonym: ppiase, rotamase, cyclophilin a. Engineered: yes. Cyclosporin a. Chain: c. Synonym: cyclosporine, ciclosporin, ciclosporine. Engineered: yes. Mutation: yes.
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: cyclophilin. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Tolypocladium inflatum. Organism_taxid: 29910
2.20Å     R-factor:   0.162    
Authors: V.Mikol,J.Kallen,M.D.Walkinshaw
Key ref: V.Mikol et al. (1994). The X-ray structure of (MeBm2t)1-cyclosporin complexed with cyclophilin A provides an explanation for its anomalously high immunosuppressive activity. Protein Eng, 7, 597-603. PubMed id: 8073029
06-Sep-95     Release date:   29-Jan-96    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P62937  (PPIA_HUMAN) -  Peptidyl-prolyl cis-trans isomerase A
165 a.a.
165 a.a.
Protein chain
No UniProt id for this chain
Struc: 11 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: Chain A: 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     extracellular region   4 terms 
  Biological process     viral reproduction   17 terms 
  Biochemical function     protein binding     6 terms  


    Added reference    
Protein Eng 7:597-603 (1994)
PubMed id: 8073029  
The X-ray structure of (MeBm2t)1-cyclosporin complexed with cyclophilin A provides an explanation for its anomalously high immunosuppressive activity.
V.Mikol, J.Kallen, M.D.Walkinshaw.
For most of the cyclosporin A (CsA) analogs, there is generally a good correlation between cyclophilin binding and immunosuppression. However, this relationship does not seem to hold for 4-[(E)-2-butenyl]-4,4,N-trimethyl-L-threonine1 (MeBm2t)1-CsA. Its affinity for cyclophilin was reported to be approximately 1% that of CsA and its immunosuppressive activity in vitro was shown to be approximately 30% that of CsA. We report here the crystal structure of a complex between recombinant human cyclophilin A (CypA) and (MeBm2t)1-CsA which has been determined by X-ray crystallography at 2.2 A resolution and refined to an R-factor of 16.3%. (MeBm2t)1-CsA shows a similar bound conformation and network of interactions to CypA as CsA. The measured lower affinity for CypA cannot therefore be explained by a different mode of binding. We propose that the poor affinity to CypA could be accounted for by the existence of an equilibrium in aqueous solution between a 'cyclophilin bound conformation' and a 'non-binding conformation' of (MeBm2t)1-CsA. The relatively high immunosuppressive activity is suggested to result from slight conformational differences observed in the effector domain.

Literature references that cite this PDB file's key reference

  PubMed id Reference
  9385632 F.F.Vajdos, S.Yoo, M.Houseweart, W.I.Sundquist, and C.P.Hill (1997).
Crystal structure of cyclophilin A complexed with a binding site peptide from the HIV-1 capsid protein.
  Protein Sci, 6, 2297-2307.
PDB codes: 1awq 1awr 1aws 1awt 1awu 1awv
  8535256 M.F.O'Donohue, A.W.Burgess, M.D.Walkinshaw, and H.R.Treutlein (1995).
Modeling conformational changes in cyclosporin A.
  Protein Sci, 4, 2191-2202.  
7866747 D.Altschuh, W.Braun, J.Kallen, V.Mikol, C.Spitzfaden, J.C.Thierry, O.Vix, M.D.Walkinshaw, and K.Wüthrich (1994).
Conformational polymorphism of cyclosporin A.
  Structure, 2, 963-972.  
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.