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PDBsum entry 1fgl
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protein Protein-protein interface(s) links
Isomerase/viral protein PDB id
1fgl

 

 

 

 

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Contents
Protein chains
165 a.a. *
12 a.a. *
Waters ×267
* Residue conservation analysis
PDB id:
1fgl
Name: Isomerase/viral protein
Title: Cyclophilin a complexed with a fragment of HIV-1 gag protein
Structure: Cyclophilin a. Chain: a. Engineered: yes. HIV-1 gag protein. Chain: b. Fragment: residues 81 - 105. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Cell_line: xa90. Gene: cyclophilin a. Expressed in: escherichia coli. Human immunodeficiency virus type 1. Virus. Organism_taxid: 11705.
Biol. unit: Dimer (from PQS)
Resolution:
1.80Å     R-factor:   0.195     R-free:   0.256
Authors: Y.Zhao,Y.Chen,M.Schutkowski,G.Fischer,H.Ke
Key ref:
Y.Zhao et al. (1997). Cyclophilin A complexed with a fragment of HIV-1 gag protein: insights into HIV-1 infectious activity. Structure, 5, 139-146. PubMed id: 9016720 DOI: 10.1016/S0969-2126(97)00172-X
Date:
18-Nov-96     Release date:   01-Apr-97    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P62937  (PPIA_HUMAN) -  Peptidyl-prolyl cis-trans isomerase A from Homo sapiens
Seq:
Struc: 		165 a.a.
165 a.a.
Protein chain
Pfam   ArchSchema ?
P05889  (GAG_HV1W2) -  Gag polyprotein (Fragment) from Human immunodeficiency virus type 1 group M subtype B (isolate WMJ22)
Seq:
Struc: 		389 a.a.
12 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: Chains A, B: E.C.5.2.1.8  - peptidylprolyl isomerase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: [protein]-peptidylproline (omega=180) = [protein]-peptidylproline (omega=0)
Peptidylproline (omega=180)
 = peptidylproline (omega=0)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 

 
    Added reference    
 
 
DOI no: 10.1016/S0969-2126(97)00172-X Structure 5:139-146 (1997)
PubMed id: 9016720  
 
 
Cyclophilin A complexed with a fragment of HIV-1 gag protein: insights into HIV-1 infectious activity.
Y.Zhao, Y.Chen, M.Schutkowski, G.Fischer, H.Ke.
 
  ABSTRACT  
 
BACKGROUND: Cyclophilin A (CyPA), a receptor of the immunosuppressive drug cyclosporin A, catalyzes the cis-trans isomerization of peptidyl-prolyl bonds and is required for the infectious activity of human immunodeficiency virus type 1 (HIV-1). The crystal structure of CyPA complexed with a fragment of the HIV-1 gag protein should provide insights into the nature of CyPA-gag interactions and may suggest a role for CyPA in HIV-1 infectious activity. RESULTS: The crystal structure of CyPA complexed with a 25 amino acid peptide of HIV-1 gag capsid protein (25-mer) was determined and refined to an R factor of 0.195 at 1.8 A resolution. The sequence Ala88-Gly89-Pro90-Ile91 of the gag fragment is the major portion to bind to the active site of CyPA. Two residues of the 25-mer (Pro90-Ile91) bind to CyPA in a similar manner to two residues (Pro-Phe) of the CyPA substrate, succinyl-Ala-Ala-Pro-Phe-p-nitroanilide (AAPF). However, the N-terminus of the 25-mer (Ala88-Gly89) exhibits a different hydrogen-bonding pattern and molecular conformation than AAPF. The peptidyl-prolyl bond between Gly89 and Pro90 of the 25-mer has a trans conformation, in contrast to the cis conformation observed in other known CyPA-peptide complexes. The residue preceding proline, Gly89, has an unfavorable backbone conformation usually only adopted by glycine. CONCLUSIONS: The unfavorable backbone conformation of Gly89 of the gag 25-mer fragment suggests that binding between HIV-1 gag protein and CyPA requires a special sequence, Gly-Pro. Thus, in HIV-1 infectivity, CyPA is likely to function as a chaperone, rather than as a cis-trans isomerase. However, the observation of similarities between the C termini of the 25-mer and the substrate AAPF means that the involvement of the cis-trans isomerase activity of CyPA cannot be completely ruled out.
 
  Selected figure(s)  
 
Figure 1.
Figure 1. Crystal structure of CyPA complexed with a fragment of HIV-1 gag protein. (a) Molecular surface charge distribution: the positively charged regions are shown in blue and negatively charged regions are in red. The 25-mer of gag capsid protein is represented in green and its sidechains are in yellow. (Figure drawn using GRASP [49].) (b) Ribbon representation: helices are shown in red, b strands in orange and loops in blue. Residues of the 25-mer are shown as a yellow stick model. (Figure plotted using the program MOLSCRIPT [50] and Raster3D [51].)
 
  The above figure is reprinted by permission from Cell Press: Structure (1997, 5, 139-146) copyright 1997.  
  Figure was selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20676357 T.L.Davis, J.R.Walker, V.Campagna-Slater, P.J.Finerty, R.Paramanathan, G.Bernstein, F.MacKenzie, W.Tempel, H.Ouyang, W.H.Lee, E.Z.Eisenmesser, and S.Dhe-Paganon (2010).
Structural and biochemical characterization of the human cyclophilin family of peptidyl-prolyl isomerases.
  PLoS Biol, 8, e1000439.
PDB codes: 1zkc 2esl 2gw2 2he9 2hq6 2r99
19825046 A.P.Mascarenhas, and K.Musier-Forsyth (2009).
The capsid protein of human immunodeficiency virus: interactions of HIV-1 capsid with host protein factors.
  FEBS J, 276, 6118-6127.  
19128175 D.Hamelberg, and J.A.McCammon (2009).
Mechanistic insight into the role of transition-state stabilization in cyclophilin A.
  J Am Chem Soc, 131, 147-152.  
19185003 S.B.Moparthi, P.Hammarström, and U.Carlsson (2009).
A nonessential role for Arg 55 in cyclophilin18 for catalysis of proline isomerization during protein folding.
  Protein Sci, 18, 475-479.  
18385230 F.Yang, J.M.Robotham, H.B.Nelson, A.Irsigler, R.Kenworthy, and H.Tang (2008).
Cyclophilin A is an essential cofactor for hepatitis C virus infection and the principal mediator of cyclosporine resistance in vitro.
  J Virol, 82, 5269-5278.  
18577167 H.Takeuchi, and T.Matano (2008).
Host factors involved in resistance to retroviral infection.
  Microbiol Immunol, 52, 318-325.  
17715216 C.Song, and C.Aiken (2007).
Analysis of human cell heterokaryons demonstrates that target cell restriction of cyclosporine-resistant human immunodeficiency virus type 1 mutants is genetically dominant.
  J Virol, 81, 11946-11956.  
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.  
  17371591 S.Abdurahman, S.Höglund, A.Höglund, and A.Vahlne (2007).
Mutation in the loop C-terminal to the cyclophilin A binding site of HIV-1 capsid protein disrupts proper virus assembly and infectivity.
  Retrovirology, 4, 19.  
17075133 D.Trzesniak, and W.F.van Gunsteren (2006).
Catalytic mechanism of cyclophilin as observed in molecular dynamics simulations: pathway prediction and reconciliation of X-ray crystallographic and NMR solution data.
  Protein Sci, 15, 2544-2551.  
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
16134115 T.J.Pemberton, and J.E.Kay (2005).
The cyclophilin repertoire of the fission yeast Schizosaccharomyces pombe.
  Yeast, 22, 927-945.  
15542632 E.Sokolskaja, D.M.Sayah, and J.Luban (2004).
Target cell cyclophilin A modulates human immunodeficiency virus type 1 infectivity.
  J Virol, 78, 12800-12808.  
12730686 B.R.Howard, F.F.Vajdos, S.Li, W.I.Sundquist, and C.P.Hill (2003).
Structural insights into the catalytic mechanism of cyclophilin A.
  Nat Struct Biol, 10, 475-481.
PDB codes: 1m9c 1m9d 1m9e 1m9f 1m9x 1m9y
11823439 D.S.Horowitz, E.J.Lee, S.A.Mabon, and T.Misteli (2002).
A cyclophilin functions in pre-mRNA splicing.
  EMBO J, 21, 470-480.  
12384371 S.Höglund, J.Su, S.S.Reneby, A.Végvári, S.Hjertén, I.M.Sintorn, H.Foster, Y.P.Wu, I.Nyström, and A.Vahlne (2002).
Tripeptide interference with human immunodeficiency virus type 1 morphogenesis.
  Antimicrob Agents Chemother, 46, 3597-3605.  
11058892 M.T.Ivery (2000).
Immunophilins: switched on protein binding domains?
  Med Res Rev, 20, 452-484.  
  9729530 H.J.de Haard, B.Kazemier, M.J.Koolen, L.J.Nijholt, R.H.Meloen, B.van Gemen, H.R.Hoogenboom, and J.W.Arends (1998).
Selection of recombinant, library-derived antibody fragments against p24 for human immunodeficiency virus type 1 diagnostics.
  Clin Diagn Lab Immunol, 5, 636-644.  
  9658084 L.Yin, D.Braaten, and J.Luban (1998).
Human immunodeficiency virus type 1 replication is modulated by host cyclophilin A expression levels.
  J Virol, 72, 6430-6436.  
9380739 A.A.Bukovsky, A.Weimann, M.A.Accola, and H.G.Göttlinger (1997).
Transfer of the HIV-1 cyclophilin-binding site to simian immunodeficiency virus from Macaca mulatta can confer both cyclosporin sensitivity and cyclosporin dependence.
  Proc Natl Acad Sci U S A, 94, 10943-10948.  
  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
  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.  
  9261445 T.Dorfman, A.Weimann, A.Borsetti, C.T.Walsh, and H.G.Göttlinger (1997).
Active-site residues of cyclophilin A are crucial for its incorporation into human immunodeficiency virus type 1 virions.
  J Virol, 71, 7110-7113.  
9374856 U.Reimer, N.el Mokdad, M.Schutkowski, and G.Fischer (1997).
Intramolecular assistance of cis/trans isomerization of the histidine-proline moiety.
  Biochemistry, 36, 13802-13808.  
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.

 

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