PDBsum entry 1oca

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Isomerase PDB id
Protein chain
165 a.a. *
* Residue conservation analysis
PDB id:
Name: Isomerase
Title: Human cyclophilin a, unligated, nmr, 20 structures
Structure: Cyclophilin a. Chain: a. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Cell: t-cell (jurkat). Gene: cyclophilin. Expressed in: escherichia coli. Expression_system_taxid: 562.
NMR struc: 20 models
Authors: M.Ottiger,O.Zerbe,P.Guntert,K.Wuthrich
Key ref:
M.Ottiger et al. (1997). The NMR solution conformation of unligated human cyclophilin A. J Mol Biol, 272, 64-81. PubMed id: 9299338 DOI: 10.1006/jmbi.1997.1220
07-Jul-97     Release date:   19-Nov-97    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P62937  (PPIA_HUMAN) -  Peptidyl-prolyl cis-trans isomerase A
165 a.a.
165 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     extracellular region   8 terms 
  Biological process     viral reproduction   18 terms 
  Biochemical function     protein binding     7 terms  


    Added reference    
DOI no: 10.1006/jmbi.1997.1220 J Mol Biol 272:64-81 (1997)
PubMed id: 9299338  
The NMR solution conformation of unligated human cyclophilin A.
M.Ottiger, O.Zerbe, P.Güntert, K.Wüthrich.
The nuclear magnetic resonance (NMR) solution structure of free, unligated cyclophilin A (CypA), which is an 18 kDa protein from human T-lymphocytes that was expressed in Escherichia coli for the present study, was determined using multidimensional heteronuclear NMR techniques. Sequence-specific resonance assignments for 99.5% of all backbone amide protons and non-labile hydrogen atoms provided the basis for collection of an input of 4101 nuclear Overhauser enhancement (NOE) upper distance constraints and 371 dihedral angle constraints for distance geometry calculations and energy minimization with the programs DIANA and OPAL. The average RMSD values of the 20 best energy-refined NMR conformers relative to the mean coordinates are 0.49 A for the backbone atoms and 0.88 A for all heavy atoms of residues 2 to 165. The molecular architecture includes an eight-stranded antiparallel beta-barrel that is closed by two amphipathic alpha-helices. Detailed comparisons with the crystal structure of free CypA revealed subtle but significant conformational differences that can in most cases be related to lattice contacts in the crystal structure. 15N spin relaxation times and NMR lineshape analyses for CypA in the free form and complexed with cyclosporin A (CsA) revealed transitions of polypeptide loops surrounding the ligand-binding site from locally flexible conformations in the free protein, some of which include well-defined conformational equilibria, to well-defined spatial arrangements in the CypA-CsA complex. Compared to the crystal structure of free CypA, where the ligand-binding area is extensively involved in lattice contacts, the NMR structure presents a highly relevant reference for studies of changes in structure and internal mobility of the binding pocket upon ligand binding, and possible consequences of this conformational variability for calcineurin recognition by the CypA-CsA complex.
  Selected figure(s)  
Figure 3.
Figure 3. Plots of the number of NOEs, global displacements (D[glob]) and crystallographic B-factors versus the amino acid sequence of CypA. (a) Numbers of NOE distance constraints per residue used in the calculation of the CypA structure. Filled, crosshatched, vertically hatched and open bars represent, respectively, intraresidual, sequential, medium-range and long-range NOEs. (b) Mean of the pairwise global displacements per residue of the backbone heavy atoms (continuous line) and all heavy atoms (broken line) of the 20 energy-minimized DIANA conformers (NMR^20) relative to the mean NMR structure ( angle bracket NMR angle bracket ) calculated after superposition of the backbone heavy atoms N, C^α and C′ of residues 2 to 165 for minimal RMSD. (c) Global displacements per residue of the backbone heavy atoms (continuous line) and all heavy atoms (broken line) between the crystal structure of free CypA [Ke 1992] and the mean NMR structure calculated after superposition of the backbone heavy atoms N, C^α and C′ of residues 2 to 165 for minimal RMSD. (d) Average temperature factors (B) per residue for the backbone heavy atoms (continuous line) and all heavy atoms (broken line) in the crystal structure [Ke 1992]. The locations of the regular secondary structure elements are given at the bottom of the Figure, where α, * and β indicate α-helix, 3[10]-helix and β-strand, respectively.
Figure 5.
Figure 5. Comparison of the NMR solution structure and the X-ray crystal structure [Ke 1992] of free CypA. (a) Stereo view of the polypeptide backbones after superposition for minimal RMSD between the heavy atoms N, C^α and C′ of residues 2 to 165. A spline function was drawn through the C^α positions. In the NMR structure (gray) the radius of the cylindrical rod corresponds to the mean of the global displacements, D[glob]^bb (Figure 3(b), among the 20 energy-minimized NMR conformers, and in the crystal structure (orange) to the converted temperature factors, Image , of the C^α atoms. In addition, the position of CsA (yellow) in the NMR structure of the CypA-CsA complex [Spitzfaden et al 1994] is shown, as obtained after superposition of the backbone heavy atoms N, C^α and C′ of residues 2 to 165 of CypA in the complex and in the free form for minimal RMSD. (b) Stereo view of the crystal contacts in the loop containing His70. The backbone and selected side-chains of the mean NMR structure (gray) and the crystal structure (orange) are shown after superposition of the backbone heavy atoms N, C^α and C′ of residues 2 to 165 for minimal RMSD. A neighboring CypA molecule in the crystal lattice is shown in dark red. Intermolecular hydrogen bonds and salt bridges between the neighboring CypA molecules in the crystal lattice are indicated with yellow broken lines. Numbers indicate the sequence positions of selected residues. (c) Stereo view of a heavy-atom representation of residues 29 to 41 and Glu86 after local superposition of the backbone heavy atoms N, C^α and C′ for minimal RMSD. The 20 DIANA conformers representing the NMR solution structure are shown in gray, and the crystal structure in orange. The residues shown form the first α-helix (residues 30 to 41) and a long-range N-cap. Helical and N-capping hydrogen bonds are represented with yellow and green broken lines, respectively (see the text for further details). (d) Stereo view of a heavy-atom representation of β-strands 4, 5 and 6 comprising residues 61 to 64, 97 to 100 and 112 to 115, respectively, after local superposition of the backbone heavy atoms N, C^α and C′ for minimal RMSD. Coloring as in (c), with the hydrogen bonds between the strands represented with yellow broken lines.
  The above figures are reprinted by permission from Elsevier: J Mol Biol (1997, 272, 64-81) copyright 1997.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
22407016 M.E.Caines, K.Bichel, A.J.Price, W.A.McEwan, G.J.Towers, B.J.Willett, S.M.Freund, and L.C.James (2012).
Diverse HIV viruses are targeted by a conformationally dynamic antiviral.
  Nat Struct Mol Biol, 19, 411-416.
PDB codes: 4dga 4dgb 4dgc 4dgd 4dge
19908896 A.Ramanathan, and P.K.Agarwal (2009).
Computational identification of slow conformational fluctuations in proteins.
  J Phys Chem B, 113, 16669-16680.  
19500591 J.Schlegel, J.S.Redzic, C.C.Porter, V.Yurchenko, M.Bukrinsky, W.Labeikovsky, G.S.Armstrong, F.Zhang, N.G.Isern, J.DeGregori, R.Hodges, and E.Z.Eisenmesser (2009).
Solution characterization of the extracellular region of CD147 and its interaction with its enzyme ligand cyclophilin A.
  J Mol Biol, 391, 518-535.  
19297321 X.Hanoulle, A.Badillo, J.M.Wieruszeski, D.Verdegem, I.Landrieu, R.Bartenschlager, F.Penin, and G.Lippens (2009).
Hepatitis C virus NS5A protein is a substrate for the peptidyl-prolyl cis/trans isomerase activity of cyclophilins A and B.
  J Biol Chem, 284, 13589-13601.  
18342330 V.Thai, P.Renesto, C.A.Fowler, D.J.Brown, T.Davis, W.Gu, D.D.Pollock, D.Kern, D.Raoult, and E.Z.Eisenmesser (2008).
Structural, biochemical, and in vivo characterization of the first virally encoded cyclophilin from the Mimivirus.
  J Mol Biol, 378, 71-86.
PDB code: 2ose
  20027201 W.Cai, Z.Xu, and A.Baumketner (2008).
A new FFT-based algorithm to compute Born radii in the generalized Born theory of biomolecule solvation.
  J Comput Phys, 227, 10162-10177.  
17848202 H.Huang, J.Zhang, W.Shen, X.Wang, J.Wu, J.Wu, and Y.Shi (2007).
Solution structure of the second bromodomain of Brd2 and its specific interaction with acetylated histone tails.
  BMC Struct Biol, 7, 57.  
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.  
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.  
16595688 C.Xu, J.Zhang, X.Huang, J.Sun, Y.Xu, Y.Tang, J.Wu, Y.Shi, Q.Huang, and Q.Zhang (2006).
Solution structure of human peptidyl prolyl isomerase-like protein 1 and insights into its interaction with SKIP.
  J Biol Chem, 281, 15900-15908.
PDB code: 1xwn
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.  
16267559 E.Z.Eisenmesser, O.Millet, W.Labeikovsky, D.M.Korzhnev, M.Wolf-Watz, D.A.Bosco, J.J.Skalicky, L.E.Kay, and D.Kern (2005).
Intrinsic dynamics of an enzyme underlies catalysis.
  Nature, 438, 117-121.  
15479237 K.Ozawa, M.J.Headlam, P.M.Schaeffer, B.R.Henderson, N.E.Dixon, and G.Otting (2004).
Optimization of an Escherichia coli system for cell-free synthesis of selectively N-labelled proteins for rapid analysis by NMR spectroscopy.
  Eur J Biochem, 271, 4084-4093.  
15340912 M.I.Zavodszky, M.Lei, M.F.Thorpe, A.R.Day, and L.A.Kuhn (2004).
Modeling correlated main-chain motions in proteins for flexible molecular recognition.
  Proteins, 57, 243-261.  
15489226 M.Katragadda, D.Morikis, and J.D.Lambris (2004).
Thermodynamic studies on the interaction of the third complement component and its inhibitor, compstatin.
  J Biol Chem, 279, 54987-54995.  
11859194 E.Z.Eisenmesser, D.A.Bosco, M.Akke, and D.Kern (2002).
Enzyme dynamics during catalysis.
  Science, 295, 1520-1523.  
11180561 A.P.Demchenko (2001).
Recognition between flexible protein molecules: induced and assisted folding.
  J Mol Recognit, 14, 42-61.  
  11206060 M.Carpentier, F.Allain, B.Haendler, M.C.Slomianny, and G.Spik (2000).
Delineation of the calcineurin-interacting region of cyclophilin B.
  Protein Sci, 9, 2386-2393.  
11058892 M.T.Ivery (2000).
Immunophilins: switched on protein binding domains?
  Med Res Rev, 20, 452-484.  
9818269 R.A.Laskowski, M.W.MacArthur, and J.M.Thornton (1998).
Validation of protein models derived from experiment.
  Curr Opin Struct Biol, 8, 631-639.  
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.