spacer
spacer

PDBsum entry 1rmh
Go to PDB code: 
protein ligands Protein-protein interface(s) links
Isomerase/ isomerase substrate PDB id
1rmh

 

 

 

 

Loading ...

 
JSmol PyMol  
Contents
Protein chains
164 a.a. *
Ligands
SIN-ALA-ALA-PRO-
PHE-NIT ×2
Waters ×114
* Residue conservation analysis
PDB id:
1rmh
Name: Isomerase/ isomerase substrate
Title: Recombinant cyclophilin a from human t cell
Structure: Cyclophilin a. Chain: a, b. Engineered: yes. Aapf peptide substrate. Chain: c, d. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Cell: t cell. Gene: cyclophilin.
Resolution:
2.40Å     R-factor:   0.189    
Authors: Y.Zhao,H.Ke
Key ref:
Y.Zhao and H.Ke (1996). Crystal structure implies that cyclophilin predominantly catalyzes the trans to cis isomerization. Biochemistry, 35, 7356-7361. PubMed id: 8652511 DOI: 10.1021/bi9602775
Date:
31-Jul-95     Release date:   14-Oct-96    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P62937  (PPIA_HUMAN) -  Peptidyl-prolyl cis-trans isomerase A from Homo sapiens
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: [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: 10.1021/bi9602775 Biochemistry 35:7356-7361 (1996)
PubMed id: 8652511  
 
 
Crystal structure implies that cyclophilin predominantly catalyzes the trans to cis isomerization.
Y.Zhao, H.Ke.
 
  ABSTRACT  
 
The crystal structure of human recombinant cyclophilin A complexed with a substrate of succinyl-Ala-Ala-Pro-Phe-p-nitroanilide (AAPF) has been determined and refined to an R-factor of 0.189 at 2.4 A resolution. The structure revealed only the cis form of the substrate bound to cyclophilin A in a stoichiometry of 1:1. This binding ratio is different from the structure of cyclophilin A complexed with the tetrapeptide N-acetyl-Ala-Ala-Pro-Ala-amidomethylcourmarin. Model docking revealed that the trans form of AAPF does not fit into the active site. The observation that only the trans cis form of AAPF binds to cyclophilin A implies that cyclophilin A predominantly catalyzes the trans to cis isomerization of a peptidylprolyl amide bond. On the basis of the structure, it is proposed that Arg55 hydrogen-bonds to the nitrogen to deconjugate the resonance of the prolyl amide bond and thus facilitates the cis-trans rotation.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21337480 C.J.Dunsmore, K.J.Malone, K.R.Bailey, M.A.Wear, H.Florance, S.Shirran, P.E.Barran, A.P.Page, M.D.Walkinshaw, and N.J.Turner (2011).
Design and synthesis of conformationally constrained cyclophilin inhibitors showing a cyclosporin-A phenotype in C. elegans.
  Chembiochem, 12, 802-810.  
20602248 A.Galat, and J.Bua (2010).
Molecular aspects of cyclophilins mediating therapeutic actions of their ligands.
  Cell Mol Life Sci, 67, 3467-3488.  
19915030 D.J.Jackson, C.McDougall, B.Woodcroft, P.Moase, R.A.Rose, M.Kube, R.Reinhardt, D.S.Rokhsar, C.Montagnani, C.Joubert, D.Piquemal, and B.M.Degnan (2010).
Parallel evolution of nacre building gene sets in molluscs.
  Mol Biol Evol, 27, 591-608.  
19327368 E.K.Asciutto, J.D.Madura, S.S.Pochapsky, B.OuYang, and T.C.Pochapsky (2009).
Structural and dynamic implications of an effector-induced backbone amide cis-trans isomerization in cytochrome P450cam.
  J Mol Biol, 388, 801-814.  
  19319933 J.Schlegel, G.S.Armstrong, J.S.Redzic, F.Zhang, and E.Z.Eisenmesser (2009).
Characterizing and controlling the inherent dynamics of cyclophilin-A.
  Protein Sci, 18, 811-824.  
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.  
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.  
19282959 V.Leone, G.Lattanzi, C.Molteni, and P.Carloni (2009).
Mechanism of action of cyclophilin a explored by metadynamics simulations.
  PLoS Comput Biol, 5, e1000309.  
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.  
18513977 B.OuYang, S.S.Pochapsky, M.Dang, and T.C.Pochapsky (2008).
A functional proline switch in cytochrome P450cam.
  Structure, 16, 916-923.  
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
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.  
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.  
16409630 P.K.Agarwal (2006).
Enzymes: An integrated view of structure, dynamics and function.
  Microb Cell Fact, 5, 2.  
16302169 X.J.Wang, and F.A.Etzkorn (2006).
Peptidyl-prolyl isomerase inhibitors.
  Biopolymers, 84, 125-146.  
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.  
15845542 K.Piotukh, W.Gu, M.Kofler, D.Labudde, V.Helms, and C.Freund (2005).
Cyclophilin A binds to linear peptide motifs containing a consensus that is present in many human proteins.
  J Biol Chem, 280, 23668-23674.  
15355356 M.Konno, Y.Sano, K.Okudaira, Y.Kawaguchi, Y.Yamagishi-Ohmori, S.Fushinobu, and H.Matsuzawa (2004).
Escherichia coli cyclophilin B binds a highly distorted form of trans-prolyl peptide isomer.
  Eur J Biochem, 271, 3794-3803.
PDB codes: 1j2a 1v9t 1vai
15210993 Q.Huai, H.Wang, W.Zhang, R.W.Colman, H.Robinson, and H.Ke (2004).
Crystal structure of phosphodiesterase 9 shows orientation variation of inhibitor 3-isobutyl-1-methylxanthine binding.
  Proc Natl Acad Sci U S A, 101, 9624-9629.
PDB codes: 1tbm 2hd1
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
11859194 E.Z.Eisenmesser, D.A.Bosco, M.Akke, and D.Kern (2002).
Enzyme dynamics during catalysis.
  Science, 295, 1520-1523.  
11859184 J.J.Falke (2002).
Enzymology. A moving story.
  Science, 295, 1480-1481.  
  11410347 J.Búa, L.Aslund, N.Pereyra, G.A.García, E.J.Bontempi, and A.M.Ruiz (2001).
Characterisation of a cyclophilin isoform in Trypanosoma cruzi.
  FEMS Microbiol Lett, 200, 43-47.  
11058892 M.T.Ivery (2000).
Immunophilins: switched on protein binding domains?
  Med Res Rev, 20, 452-484.  
9465090 B.Sherry, G.Zybarth, M.Alfano, L.Dubrovsky, R.Mitchell, D.Rich, P.Ulrich, R.Bucala, A.Cerami, and M.Bukrinsky (1998).
Role of cyclophilin A in the uptake of HIV-1 by macrophages and T lymphocytes.
  Proc Natl Acad Sci U S A, 95, 1758-1763.  
  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.  
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
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
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 code is shown on the right.

 

spacer
spacer