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PDBsum entry 2cpl

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protein links
Isomerase(peptidyl-prolyl cis-trans) PDB id
2cpl
Jmol
Contents
Protein chain
164 a.a. *
Waters ×119
* Residue conservation analysis
PDB id:
2cpl
Name: Isomerase(peptidyl-prolyl cis-trans)
Title: Similarities and differences between human cyclophilin a and other beta-barrel structures. Structural refinement at 1.63 angstroms resolution
Structure: Cyclophilin a. Chain: a. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: cyclophilin.
Resolution:
1.63Å     R-factor:   0.180    
Authors: H.Ke
Key ref:
H.Ke (1992). Similarities and differences between human cyclophilin A and other beta-barrel structures. Structural refinement at 1.63 A resolution. J Mol Biol, 228, 539-550. PubMed id: 1453463 DOI: 10.1016/0022-2836(92)90841-7
Date:
30-Jun-92     Release date:   31-Oct-93    
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.
164 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     extracellular region   8 terms 
  Biological process     viral reproduction   18 terms 
  Biochemical function     protein binding     7 terms  

 

 
    Added reference    
 
 
DOI no: 10.1016/0022-2836(92)90841-7 J Mol Biol 228:539-550 (1992)
PubMed id: 1453463  
 
 
Similarities and differences between human cyclophilin A and other beta-barrel structures. Structural refinement at 1.63 A resolution.
H.Ke.
 
  ABSTRACT  
 
The structure of the unligated recombinant human cyclophilin A (CyP A) has been refined to an R-factor of 0.18 at 1.63 A resolution. The root-mean-squared deviations of the refined structure are 0.013 A and 2.50 degrees from ideal geometries of bond length and bond angle, respectively. Eight antiparallel beta-strands of CyP A form a right-handed beta-barrel. The structure of CyP A is compared with other members in the antiparallel eight-stranded beta-barrel family and with the parallel eight-stranded alpha/beta barrels. Although all known eight-stranded barrels are right-handed, the tilted angle of the strands against the barrel axis varies from 45 degrees for retinol binding protein and 49 degrees for CyP A to 70 degrees for superoxide dismutase. As a result, the beta-barrel of CyP A is not completely superimposable with other members of beta-barrels. The structure of CyP A has a unique topology, distinct from other members in the beta-barrel family. In addition, CyP A is a closed beta-barrel so that neither the immunosuppressive drug cyclosporin A (CsA) nor the proline-containing substrate can bind to the hydrophobic core of the CyP A barrel, while the hydrophobic core of most other barrels is open for ligation. These observations probably indicate that CyP A is neither functionally nor evolutionally related to other beta-barrel structures. Details of interactions between solvent molecules and the active site residues of CyP A are illustrated. A water-co-operated mechanism, where the cis<-->trans isomerization might possibly consist of (1) transition of the prolyl bond and (2) release of N or C-terminal residues of substrate from CyP, is addressed. The refined structure reveals no disulfide bridges in CyP A. Cys115 is near the CsA site, but unlikely to be directly involved in CsA binding because of steric hindrance from Thr119 and Leu122. This geometry probably rules out any mechanisms involving a tetrahedral intermediate formed between cysteine and substrate during cis<-->trans isomerization.
 
  Selected figure(s)  
 
Figure 4.
Figure 4. A schematic diagram of the secondary struc- ture of human CyP A. N and C represent te 1v- and C: termini, respectively. Helices are shown as cylinders and b-strands as arrows. The B-barrel as dimensions of about 14 A for height, and 15 and 17 A for the minor and major xes of the elliptical cross ection of the barrel. Helices: strands an turns are 21%, 36% and 10% of the total amino acid residues, respectively. The hydrophobic core of he barrel is closed by helices H2 and H4 so that ligands are predicted to bind at the surfaces of the barrel.
Figure 8.
Figure 8. Schematic presentation of B-barrels. Takig a -barrel as non-ideal cylinder, a and b represent the major and mior axes of the elliptical cross-section of the arrel while h is the height. Angle 0 is the tilted angle etween /l-strands and the barrel axis. A right-handed arrel has < 90'' while a left-handed barrel has fI > 90''.
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (1992, 228, 539-550) copyright 1992.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
22334143 L.Davis, and J.W.Chin (2012).
Designer proteins: applications of genetic code expansion in cell biology.
  Nat Rev Mol Cell Biol, 13, 168-182.  
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
20364129 M.Lammers, H.Neumann, J.W.Chin, and L.C.James (2010).
Acetylation regulates cyclophilin A catalysis, immunosuppression and HIV isomerization.
  Nat Chem Biol, 6, 331-337.
PDB codes: 2x25 2x2a 2x2c 2x2d
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
18065652 J.Stie, and D.Fox (2008).
Calcineurin regulation in fungi and beyond.
  Eukaryot Cell, 7, 177-186.  
18154373 E.F.Koslover, and D.J.Wales (2007).
Geometry optimization for peptides and proteins: Comparison of Cartesian and internal coordinates.
  J Chem Phys, 127, 234105.  
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
16968222 G.Coaker, G.Zhu, Z.Ding, S.R.Van Doren, and B.Staskawicz (2006).
Eukaryotic cyclophilin as a molecular switch for effector activation.
  Mol Microbiol, 61, 1485-1496.  
16700961 M.Potenza, A.Galat, T.A.Minning, A.M.Ruiz, R.Duran, R.L.Tarleton, M.Marín, L.E.Fichera, and J.Búa (2006).
Analysis of the Trypanosoma cruzi cyclophilin gene family and identification of Cyclosporin A binding proteins.
  Parasitology, 132, 867-882.  
16231289 H.Li, A.D.Robertson, and J.H.Jensen (2005).
Very fast empirical prediction and rationalization of protein pKa values.
  Proteins, 61, 704-721.  
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
15955073 K.Ozawa, M.J.Headlam, D.Mouradov, S.J.Watt, J.L.Beck, K.J.Rodgers, R.T.Dean, T.Huber, G.Otting, and N.E.Dixon (2005).
Translational incorporation of L-3,4-dihydroxyphenylalanine into proteins.
  FEBS J, 272, 3162-3171.  
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
15281132 A.Galat (2004).
Function-dependent clustering of orthologues and paralogues of cyclophilins.
  Proteins, 56, 808-820.  
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.  
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.  
11058892 M.T.Ivery (2000).
Immunophilins: switched on protein binding domains?
  Med Res Rev, 20, 452-484.  
10713041 U.Reidt, K.Reuter, T.Achsel, D.Ingelfinger, R.Lührmann, and R.Ficner (2000).
Crystal structure of the human U4/U6 small nuclear ribonucleoprotein particle-specific SnuCyp-20, a nuclear cyclophilin.
  J Biol Chem, 275, 7439-7442.
PDB code: 1qoi
  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
9241431 C.Chothia, T.Hubbard, S.Brenner, H.Barns, and A.Murzin (1997).
Protein folds in the all-beta and all-alpha classes.
  Annu Rev Biophys Biomol Struct, 26, 597-627.  
  9032343 D.Braaten, H.Ansari, and J.Luban (1997).
The hydrophobic pocket of cyclophilin is the binding site for the human immunodeficiency virus type 1 Gag polyprotein.
  J Virol, 71, 2107-2113.  
  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
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
  8762132 A.C.Wallace, R.A.Laskowski, and J.M.Thornton (1996).
Derivation of 3D coordinate templates for searching structural databases: application to Ser-His-Asp catalytic triads in the serine proteinases and lipases.
  Protein Sci, 5, 1001-1013.  
8612612 A.Galat (1996).
A note on circular-dichroic-constrained prediction of protein secondary structure.
  Eur J Biochem, 236, 428-435.  
9162944 L.Zhang, and J.Hermans (1996).
Hydrophilicity of cavities in proteins.
  Proteins, 24, 433-438.  
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
7878731 K.E.Rudd, H.J.Sofia, E.V.Koonin, G.Plunkett, S.Lazar, and P.E.Rouviere (1995).
A new family of peptidyl-prolyl isomerases.
  Trends Biochem Sci, 20, 12-14.  
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.  
7669915 P.Gallo, M.Saviano, F.Rossi, V.Pavone, C.Pedone, R.Ragone, P.Stiuso, and G.Colonna (1995).
Specific interaction between cyclophilin and cyclic peptides.
  Biopolymers, 36, 273-281.  
8075536 C.Spitzfaden, W.Braun, G.Wider, H.Widmer, and K.Wüthrich (1994).
Determination of the NMR solution structure of the cyclophilin A-cyclosporin A complex.
  J Biomol NMR, 4, 463-482.
PDB code: 3cys
8075981 H.Ke, D.Mayrose, P.J.Belshaw, D.G.Alberg, S.L.Schreiber, Z.Y.Chang, F.A.Etzkorn, S.Ho, and C.T.Walsh (1994).
Crystal structures of cyclophilin A complexed with cyclosporin A and N-methyl-4-[(E)-2-butenyl]-4,4-dimethylthreonine cyclosporin A.
  Structure, 2, 33-44.
PDB codes: 2rma 2rmb
8404888 A.Galat (1993).
Peptidylproline cis-trans-isomerases: immunophilins.
  Eur J Biochem, 216, 689-707.  
8335079 H.Bang, K.Brune, C.Nager, and U.Feige (1993).
Interleukin-8 is a cyclosporin A binding protein.
  Experientia, 49, 533-538.  
8475075 H.Ke, D.Mayrose, and W.Cao (1993).
Crystal structure of cyclophilin A complexed with substrate Ala-Pro suggests a solvent-assisted mechanism of cis-trans isomerization.
  Proc Natl Acad Sci U S A, 90, 3324-3328.
PDB code: 1cyh
8265636 H.Ke, Y.Zhao, F.Luo, I.Weissman, and J.Friedman (1993).
Crystal structure of murine cyclophilin C complexed with immunosuppressive drug cyclosporin A.
  Proc Natl Acad Sci U S A, 90, 11850-11854.
PDB code: 2rmc
8212315 M.A.Navia, and D.A.Peattie (1993).
Structure-based drug design: applications in immunopharmacology and immunosuppression.
  Trends Pharmacol Sci, 14, 189-195.  
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