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PDBsum entry 1awr

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Complex (isomerase/peptide) PDB id
1awr
Jmol
Contents
Protein chains
(+ 0 more) 164 a.a. *
Ligands
HIS-ALA-GLY-PRO-
ILE-ALA
×6
Waters ×175
* Residue conservation analysis
PDB id:
1awr
Name: Complex (isomerase/peptide)
Title: Cypa complexed with hagpia
Structure: Cyclophilin a. Chain: a, b, c, d, e, f. Engineered: yes. Peptide from the HIV-1 capsid protein. Chain: g, h, i, j, k, l. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Cellular_location: cytoplasm. Gene: cyclophilin. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
1.58Å     R-factor:   0.394     R-free:   0.461
Authors: F.F.Vajdos
Key ref:
F.F.Vajdos et al. (1997). Crystal structure of cyclophilin A complexed with a binding site peptide from the HIV-1 capsid protein. Protein Sci, 6, 2297-2307. PubMed id: 9385632 DOI: 10.1002/pro.5560061103
Date:
04-Oct-97     Release date:   18-Mar-98    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
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: 10.1002/pro.5560061103 Protein Sci 6:2297-2307 (1997)
PubMed id: 9385632  
 
 
Crystal structure of cyclophilin A complexed with a binding site peptide from the HIV-1 capsid protein.
F.F.Vajdos, S.Yoo, M.Houseweart, W.I.Sundquist, C.P.Hill.
 
  ABSTRACT  
 
The cellular protein, cyclophilin A (CypA), is incorporated into the virion of the type 1 human immunodeficiency virus (HIV-1) via a direct interaction with the capsid domain of the viral Gag polyprotein. We demonstrate that the capsid sequence 87His-Ala-Gly-Pro-Ile-Ala92 (87HAGPIA92) encompasses the primary cyclophilin A binding site and present an X-ray crystal structure of the CypA/HAGPIA complex. In contrast to the cis prolines observed in all previously reported structures of CypA complexed with model peptides, the proline in this peptide, Pro 90, binds the cyclophilin A active site in a trans conformation. We also report the crystal structure of a complex between CypA and the hexapeptide HVGPIA, which also maintains the trans conformation. Comparison with the recently determined structures of CypA in complexes with larger fragments of the HIV-1 capsid protein demonstrates that CypA recognition of these hexapeptides involves contacts with peptide residues Ala(Val) 88, Gly 89, and Pro 90, and is independent of the context of longer sequences.
 
  Selected figure(s)  
 
Figure 6.
Fig. 6. A: HAGPIA and CypA are shown in CPK and ribbon representa- tions, respectively. B: Orthogonal view. C: The molecular surface of CypA is colored gray and green according to curvature. CypA residues that in- teract with HAGPIA are shown, and residues that hydrogen bond (magen- ta) HAGPIA re in yellow. H drogen bonds are defined as acceptor to donor distances of less than 3.3 x. The HAGPIA N-terminal histidine and C-terminal alanine are labeled in For clarity, the side chains f the histidine and isoleucine have been omitted. Two ordered water that form bridging hydrogen bonds between peptide main chain and CypA active site residues are shown as blue spheres.
Figure 7.
Fig. 7. Superposition of HAGPIA and peptides refined in the pseudo (P4~)-cell. CypA CA atoms (residues 2-165) were overlapped by least squares (Kabsch, 976). CypA residues that hydrogen bond pep- tide ligands are HAGPIA (magenta), (cyan). Ala/Val 88 and the peptide proline residues are labeled.
 
  The above figures are reprinted from an Open Access publication published by the Protein Society: Protein Sci (1997, 6, 2297-2307) 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
20602248 A.Galat, and J.Bua (2010).
Molecular aspects of cyclophilins mediating therapeutic actions of their ligands.
  Cell Mol Life Sci, 67, 3467-3488.  
20445238 A.H.Robbins, J.F.Domsic, M.Agbandje-McKenna, and R.McKenna (2010).
Structure of a monoclinic polymorph of human carbonic anhydrase II with a doubled a axis.
  Acta Crystallogr D Biol Crystallogr, 66, 628-634.
PDB code: 3ks1
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.  
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.  
19908896 A.Ramanathan, and P.K.Agarwal (2009).
Computational identification of slow conformational fluctuations in proteins.
  J Phys Chem B, 113, 16669-16680.  
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.  
19465766 M.Guelker, L.Stagg, P.Wittung-Stafshede, and Y.Shamoo (2009).
Pseudosymmetry, high copy number and twinning complicate the structure determination of Desulfovibrio desulfuricans (ATCC 29577) flavodoxin.
  Acta Crystallogr D Biol Crystallogr, 65, 523-534.
PDB codes: 3f6r 3f6s
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.  
18057233 H.O.Peters, M.G.Mendoza, R.E.Capina, M.Luo, X.Mao, M.Gubbins, N.J.Nagelkerke, I.Macarthur, B.B.Sheardown, J.Kimani, C.Wachihi, S.Thavaneswaran, and F.A.Plummer (2008).
An integrative bioinformatic approach for studying escape mutations in human immunodeficiency virus type 1 gag in the Pumwani Sex Worker Cohort.
  J Virol, 82, 1980-1992.  
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.  
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.  
17299408 M.A.Rits, K.A.van Dort, C.Münk, A.B.Meijer, and N.A.Kootstra (2007).
Efficient transduction of simian cells by HIV-1-based lentiviral vectors that contain mutations in the capsid protein.
  Mol Ther, 15, 930-937.  
  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.  
17372357 T.J.Oldfield (2007).
CAALIGN: a program for pairwise and multiple protein-structure alignment.
  Acta Crystallogr D Biol Crystallogr, 63, 514-525.  
  17277440 V.Venugopal, B.Sen, A.K.Datta, and R.Banerjee (2007).
Structure of cyclophilin from Leishmania donovani at 1.97 A resolution.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 63, 60-64.
PDB code: 2haq
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.  
17057340 E.Oksanen, V.P.Jaakola, T.Tolonen, K.Valkonen, B.Akerström, N.Kalkkinen, V.Virtanen, and A.Goldman (2006).
Reindeer beta-lactoglobulin crystal structure with pseudo-body-centred noncrystallographic symmetry.
  Acta Crystallogr D Biol Crystallogr, 62, 1369-1374.
PDB code: 1yup
16409630 P.K.Agarwal (2006).
Enzymes: An integrated view of structure, dynamics and function.
  Microb Cell Fact, 5, 2.  
16254380 C.C.Mische, H.Javanbakht, B.Song, F.Diaz-Griffero, M.Stremlau, B.Strack, Z.Si, and J.Sodroski (2005).
Retroviral restriction factor TRIM5alpha is a trimer.
  J Virol, 79, 14446-14450.  
16174436 H.X.Guo, F.Wang, K.Q.Yu, J.Chen, D.L.Bai, K.X.Chen, X.Shen, and H.L.Jiang (2005).
Novel cyclophilin D inhibitors derived from quinoxaline exhibit highly inhibitory activity against rat mitochondrial swelling and Ca2+ uptake/ release.
  Acta Pharmacol Sin, 26, 1201-1211.  
15388925 A.Korostelev, M.O.Fenley, and M.S.Chapman (2004).
Impact of a Poisson-Boltzmann electrostatic restraint on protein structures refined at medium resolution.
  Acta Crystallogr D Biol Crystallogr, 60, 1786-1794.  
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.  
15479239 L.M.Henriksson, P.Johansson, T.Unge, and S.L.Mowbray (2004).
X-ray structure of peptidyl-prolyl cis-trans isomerase A from Mycobacterium tuberculosis.
  Eur J Biochem, 271, 4107-4113.
PDB code: 1w74
15229879 P.K.Agarwal (2004).
Cis/trans isomerization in HIV-1 capsid protein catalyzed by cyclophilin A: insights from computational and theoretical studies.
  Proteins, 56, 449-463.  
15568972 S.P.Goff (2004).
Genetic control of retrovirus susceptibility in mammalian cells.
  Annu Rev Genet, 38, 61-85.  
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
12832754 J.E.Padilla, and T.O.Yeates (2003).
A statistic for local intensity differences: robustness to anisotropy and pseudo-centering and utility for detecting twinning.
  Acta Crystallogr D Biol Crystallogr, 59, 1124-1130.  
14646082 T.R.Barends, and B.W.Dijkstra (2003).
Acetobacter turbidans alpha-amino acid ester hydrolase: merohedral twinning in P21 obscured by pseudo-translational NCS.
  Acta Crystallogr D Biol Crystallogr, 59, 2237-2241.  
11836403 A.C.Saphire, M.D.Bobardt, and P.A.Gallay (2002).
trans-Complementation rescue of cyclophilin A-deficient viruses reveals that the requirement for cyclophilin A in human immunodeficiency virus type 1 replication is independent of its isomerase activity.
  J Virol, 76, 2255-2262.  
12021440 F.Fabiola, R.Bertram, A.Korostelev, and M.S.Chapman (2002).
An improved hydrogen bond potential: impact on medium resolution protein structures.
  Protein Sci, 11, 1415-1423.  
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.  
11713476 F.Poy, M.Lepourcelet, R.A.Shivdasani, and M.J.Eck (2001).
Structure of a human Tcf4-beta-catenin complex.
  Nat Struct Biol, 8, 1053-1057.
PDB code: 1jpw
11312344 L.Dietrich, L.S.Ehrlich, T.J.LaGrassa, D.Ebbets-Reed, and C.Carter (2001).
Structural consequences of cyclophilin A binding on maturational refolding in human immunodeficiency virus type 1 capsid protein.
  J Virol, 75, 4721-4733.  
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.