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PDBsum entry 1cwa

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protein Protein-protein interface(s) links
Isomerase/immunosuppressant PDB id
1cwa
Jmol
Contents
Protein chains
165 a.a. *
11 a.a. *
Waters ×144
* Residue conservation analysis
PDB id:
1cwa
Name: Isomerase/immunosuppressant
Title: X-ray structure of a monomeric cyclophilin a-cyclosporin a c complex at 2.1 angstroms resolution
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
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: cyclophilin. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Tolypocladium inflatum. Organism_taxid: 29910
Resolution:
2.10Å     R-factor:   0.167    
Authors: V.Mikol,J.Kallen,M.D.Walkinshaw
Key ref: V.Mikol et al. (1993). X-ray structure of a monomeric cyclophilin A-cyclosporin A crystal complex at 2.1 A resolution. J Mol Biol, 234, 1119-1130. PubMed id: 8263916 DOI: 10.1006/jmbi.1993.1664
Date:
06-Sep-95     Release date:   29-Jan-96    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P62937  (PPIA_HUMAN) -  Peptidyl-prolyl cis-trans isomerase A
Seq:
Struc:
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.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     extracellular region   5 terms 
  Biological process     viral reproduction   18 terms 
  Biochemical function     protein binding     7 terms  

 

 
    Added reference    
 
 
DOI no: 10.1006/jmbi.1993.1664 J Mol Biol 234:1119-1130 (1993)
PubMed id: 8263916  
 
 
X-ray structure of a monomeric cyclophilin A-cyclosporin A crystal complex at 2.1 A resolution.
V.Mikol, J.Kallen, G.Pflügl, M.D.Walkinshaw.
 
  ABSTRACT  
 
The crystal structure of a complex between recombinant human cyclophilin A (Cyp) and cyclosporin A (CsA) has been determined from a novel orthorhombic crystal form that contains only one monomer of complex per asymmetric unit rather than five in the previously determined tetragonal structure. The structure has been refined at 2.1 A resolution to a crystallographic R-factor of 16.7%. The conformation of Cyp is practically unchanged with respect to the tetragonal form. A certain number of previously undefined side-chains have been located in the electron density and a very detailed picture of the ordered solvent structure has been obtained. The interactions between CsA and Cyp are conserved. A network of the possibly conserved, water-mediated contacts is described. The structure of CsA in the monomeric complex is similar to that of the decameric complex, but shows a few small differences in the so-called effector domain of CsA, probably due to differences in crystal environment. The fact that this monomeric crystal form can be obtained shows that the formation of pentamer or decamer complexes is not a generally observed phenomenon and is not a prerequisite for biological activity.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21245533 A.Kuglstatter, F.Mueller, E.Kusznir, B.Gsell, M.Stihle, R.Thoma, J.Benz, L.Aspeslet, D.Freitag, and M.Hennig (2011).
Structural basis for the cyclophilin A binding affinity and immunosuppressive potency of E-ISA247 (voclosporin).
  Acta Crystallogr D Biol Crystallogr, 67, 119-123.
PDB codes: 3odi 3odl
20602248 A.Galat, and J.Bua (2010).
Molecular aspects of cyclophilins mediating therapeutic actions of their ligands.
  Cell Mol Life Sci, 67, 3467-3488.  
20368803 C.M.Stegmann, R.Lührmann, and M.C.Wahl (2010).
The crystal structure of PPIL1 bound to cyclosporine A suggests a binding mode for a linear epitope of the SKIP protein.
  PLoS One, 5, e10013.
PDB code: 2x7k
19237751 S.K.Johnas, B.Dittrich, A.Meents, M.Messerschmidt, and E.F.Weckert (2009).
Charge-density study on cyclosporine A.
  Acta Crystallogr D Biol Crystallogr, 65, 284-293.  
19923714 V.Venugopal, A.K.Datta, D.Bhattacharyya, D.Dasgupta, and R.Banerjee (2009).
Structure of cyclophilin from Leishmania donovani bound to cyclosporin at 2.6 A resolution: correlation between structure and thermodynamic data.
  Acta Crystallogr D Biol Crystallogr, 65, 1187-1195.
PDB code: 3eov
18076075 K.Kajitani, M.Fujihashi, Y.Kobayashi, S.Shimizu, Y.Tsujimoto, and K.Miki (2008).
Crystal structure of human cyclophilin D in complex with its inhibitor, cyclosporin A at 0.96-A resolution.
  Proteins, 70, 1635-1639.
PDB code: 2z6w
17225137 P.Mark, and L.Nilsson (2007).
A molecular dynamics study of Cyclophilin A free and in complex with the Ala-Pro dipeptide.
  Eur Biophys J, 36, 213-224.  
17449029 S.Chen, X.Zhao, J.Tan, H.Lu, Z.Qi, Q.Huang, X.Zeng, M.Zhang, S.Jiang, H.Jiang, and L.Yu (2007).
Structure-based identification of small molecule compounds targeting cell cyclophilin A with anti-HIV-1 activity.
  Eur J Pharmacol, 565, 54-59.  
17855358 X.Hanoulle, A.Melchior, N.Sibille, B.Parent, A.Denys, J.M.Wieruszeski, D.Horvath, F.Allain, G.Lippens, and I.Landrieu (2007).
Structural and functional characterization of the interaction between cyclophilin B and a heparin-derived oligosaccharide.
  J Biol Chem, 282, 34148-34158.  
17242738 Z.Li, and T.Lazaridis (2007).
Water at biomolecular binding interfaces.
  Phys Chem Chem Phys, 9, 573-581.  
17103061 A.Manteca, A.I.Pelaez, R.Zardoya, and J.Sanchez (2006).
Actinobacteria cyclophilins: phylogenetic relationships and description of new class- and order-specific paralogues.
  J Mol Evol, 63, 719-732.  
16372262 P.Ghezzi, S.Casagrande, T.Massignan, M.Basso, E.Bellacchio, L.Mollica, E.Biasini, R.Tonelli, I.Eberini, E.Gianazza, W.W.Dai, M.Fratelli, M.Salmona, B.Sherry, and V.Bonetto (2006).
Redox regulation of cyclophilin A by glutathionylation.
  Proteomics, 6, 817-825.  
16260779 P.W.Hermans, P.V.Adrian, C.Albert, S.Estevão, T.Hoogenboezem, I.H.Luijendijk, T.Kamphausen, and S.Hammerschmidt (2006).
The streptococcal lipoprotein rotamase A (SlrA) is a functional peptidyl-prolyl isomerase involved in pneumococcal colonization.
  J Biol Chem, 281, 968-976.  
15772070 J.Kallen, R.Sedrani, G.Zenke, and J.Wagner (2005).
Structure of human cyclophilin A in complex with the novel immunosuppressant sanglifehrin A at 1.6 A resolution.
  J Biol Chem, 280, 21965-21971.
PDB code: 1ynd
15735342 L.L.Huang, X.M.Zhao, C.Q.Huang, L.Yu, and Z.X.Xia (2005).
Structure of recombinant human cyclophilin J, a novel member of the cyclophilin family.
  Acta Crystallogr D Biol Crystallogr, 61, 316-321.
PDB code: 1xyh
15706440 Q.Yao, M.Li, H.Yang, H.Chai, W.Fisher, and C.Chen (2005).
Roles of cyclophilins in cancers and other organ systems.
  World J Surg, 29, 276-280.  
15572368 Y.Zhang, F.Erdmann, R.Baumgrass, M.Schutkowski, and G.Fischer (2005).
Unexpected side chain effects at residue 8 of cyclosporin a derivatives allow photoswitching of immunosuppression.
  J Biol Chem, 280, 4842-4850.  
15308100 J.Colgan, M.Asmal, M.Neagu, B.Yu, J.Schneidkraut, Y.Lee, E.Sokolskaja, A.Andreotti, and J.Luban (2004).
Cyclophilin A regulates TCR signal strength in CD4+ T cells via a proline-directed conformational switch in Itk.
  Immunity, 21, 189-201.  
14755575 L.A.Bodack, T.B.Freedman, B.Z.Chowdhry, and L.A.Nafie (2004).
Solution conformations of cyclosporins and magnesium-cyclosporin complexes determined by vibrational circular dichroism.
  Biopolymers, 73, 163-177.  
14583619 R.Baumgrass, Y.Zhang, F.Erdmann, A.Thiel, M.Weiwad, A.Radbruch, and G.Fischer (2004).
Substitution in position 3 of cyclosporin A abolishes the cyclophilin-mediated gain-of-function mechanism but not immunosuppression.
  J Biol Chem, 279, 2470-2479.  
15239062 Y.Zhang, R.Baumgrass, R.Raumgrass, M.Schutkowski, and G.Fischer (2004).
Branches on the alpha-C atom of cyclosporin A residue 3 result in direct calcineurin inhibition and rapid cyclophilin 18 binding.
  Chembiochem, 5, 1006-1009.  
12644988 M.Kipping, and A.Schierhorn (2003).
Improving hydrogen/deuterium exchange mass spectrometry by reduction of the back-exchange effect.
  J Mass Spectrom, 38, 271-276.  
12447904 D.Altschuh (2002).
Cyclosporin A as a model antigen: immunochemical and structural studies.
  J Mol Recognit, 15, 277-285.  
12357034 L.Jin, and S.C.Harrison (2002).
Crystal structure of human calcineurin complexed with cyclosporin A and human cyclophilin.
  Proc Natl Acad Sci U S A, 99, 13522-13526.
PDB code: 1mf8
12052773 P.E.Shaw (2002).
Peptidyl-prolyl isomerases: a new twist to transcription.
  EMBO Rep, 3, 521-526.  
12351834 R.Banerjee, M.Dutta, M.Sen, and A.K.Datta (2002).
Crystallization and preliminary X-ray analysis of cyclophilin from Leishmania donovani.
  Acta Crystallogr D Biol Crystallogr, 58, 1846-1847.  
11250896 D.Braaten, and J.Luban (2001).
Cyclophilin A regulates HIV-1 infectivity, as demonstrated by gene targeting in human T cells.
  EMBO J, 20, 1300-1309.  
11576329 P.Sedmera, A.Jegorov, M.Buchta, and L.Cvak (2001).
11-Demethylcyclosporins exhibit a single conformation in methanol and dimethylsulfoxide.
  J Pept Res, 58, 229-236.  
10602736 M.C.Cruz, M.Del Poeta, P.Wang, R.Wenger, G.Zenke, V.F.Quesniaux, N.R.Movva, J.R.Perfect, M.E.Cardenas, and J.Heitman (2000).
Immunosuppressive and nonimmunosuppressive cyclosporine analogs are toxic to the opportunistic fungal pathogen Cryptococcus neoformans via cyclophilin-dependent inhibition of calcineurin.
  Antimicrob Agents Chemother, 44, 143-149.  
11058892 M.T.Ivery (2000).
Immunophilins: switched on protein binding domains?
  Med Res Rev, 20, 452-484.  
10642184 P.J.Ellis, C.K.Carlow, D.Ma, and P.Kuhn (2000).
Crystal structure of the complex of brugia malayi cyclophilin and cyclosporin A.
  Biochemistry, 39, 592-598.
PDB codes: 1c5f 1qtl
10382674 M.Gastmans, G.Volckaert, and Y.Engelborghs (1999).
Tryptophan microstate reshuffling upon the binding of cyclosporin A to human cyclophilin A.
  Proteins, 35, 464-474.  
  10422840 R.Golbik, G.Fischer, and A.R.Fersht (1999).
Folding of barstar C40A/C82A/P27A and catalysis of the peptidyl-prolyl cis/trans isomerization by human cytosolic cyclophilin (Cyp18).
  Protein Sci, 8, 1505-1514.  
9559680 P.Taylor, A.P.Page, G.Kontopidis, H.Husi, and M.D.Walkinshaw (1998).
The X-ray structure of a divergent cyclophilin from the nematode parasite Brugia malayi.
  FEBS Lett, 425, 361-366.
PDB code: 1a58
  9570313 S.Teigelkamp, T.Achsel, C.Mundt, S.F.Göthel, U.Cronshagen, W.S.Lane, M.Marahiel, and R.Lührmann (1998).
The 20kD protein of human [U4/U6.U5] tri-snRNPs is a novel cyclophilin that forms a complex with the U4/U6-specific 60kD and 90kD proteins.
  RNA, 4, 127-141.  
  9655334 V.Mikol, D.Ma, and C.K.Carlow (1998).
Crystal structure of the cyclophilin-like domain from the parasitic nematode Brugia malayi.
  Protein Sci, 7, 1310-1316.
PDB code: 1a33
  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.  
9016720 Y.Zhao, Y.Chen, M.Schutkowski, G.Fischer, and H.Ke (1997).
Cyclophilin A complexed with a fragment of HIV-1 gag protein: insights into HIV-1 infectious activity.
  Structure, 5, 139-146.
PDB code: 1fgl
  8676452 J.Colgan, H.E.Yuan, E.K.Franke, and J.Luban (1996).
Binding of the human immunodeficiency virus type 1 Gag polyprotein to cyclophilin A is mediated by the central region of capsid and requires Gag dimerization.
  J Virol, 70, 4299-4310.  
8994885 M.A.Navia (1996).
Protein-drug complexes important for immunoregulation and organ transplantation.
  Curr Opin Struct Biol, 6, 838-847.  
8541448 M.Marraud, and A.Aubry (1996).
Crystal structures of peptides and modified peptides.
  Biopolymers, 40, 45-83.  
9101762 P.Taylor, V.Mikol, J.Kallen, P.Burkhard, and M.D.Walkinshaw (1996).
Conformational polymorphism in peptidic and nonpeptidic drug molecules.
  Biopolymers, 40, 585-592.  
8652511 Y.Zhao, and H.Ke (1996).
Crystal structure implies that cyclophilin predominantly catalyzes the trans to cis isomerization.
  Biochemistry, 35, 7356-7361.
PDB code: 1rmh
8652512 Y.Zhao, and H.Ke (1996).
Mechanistic implication of crystal structures of the cyclophilin-dipeptide complexes.
  Biochemistry, 35, 7362-7368.
PDB codes: 2cyh 3cyh 4cyh 5cyh
7744028 K.Hoffmann, L.T.Kakalis, K.S.Anderson, I.M.Armitage, and R.E.Handschumacher (1995).
Expression of human cyclophilin-40 and the effect of the His141-->Trp mutation on catalysis and cyclosporin A binding.
  Eur J Biochem, 229, 188-193.  
12506411 K.Yamamoto, N.Kurokawa, M.Kadobayashi, N.Tauchi, K.Iguchi, N.Yanaihara, and C.Yanaihara (1995).
Mapping of cyclosporin A binding sites in cyclophilin A by using synthetic peptides.
  Regul Pept, 59, 23-30.  
7673124 M.E.Cardenas, E.Lim, and J.Heitman (1995).
Mutations that perturb cyclophilin A ligand binding pocket confer cyclosporin A resistance in Saccharomyces cerevisiae.
  J Biol Chem, 270, 20997-21002.  
7777516 S.R.Bartz, E.Hohenwalter, M.K.Hu, D.H.Rich, and M.Malkovsky (1995).
Inhibition of human immunodeficiency virus replication by nonimmunosuppressive analogs of cyclosporin A.
  Proc Natl Acad Sci U S A, 92, 5381-5385.  
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.  
8197205 V.Mikol, J.Kallen, and M.D.Walkinshaw (1994).
X-ray structure of a cyclophilin B/cyclosporin complex: comparison with cyclophilin A and delineation of its calcineurin-binding domain.
  Proc Natl Acad Sci U S A, 91, 5183-5186.
PDB code: 1cyn
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