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PDBsum entry 3cyh

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Isomerase PDB id
3cyh
Jmol
Contents
Protein chain
164 a.a. *
Ligands
SER-PRO
Waters ×162
* Residue conservation analysis
PDB id:
3cyh
Name: Isomerase
Title: Cyclophilin a complexed with dipeptide ser-pro
Structure: Cyclophilin a. Chain: a. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Cell_line: xa90. Gene: cyclophilin. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
1.90Å     R-factor:   0.191    
Authors: Y.Zhao,H.Ke
Key ref:
Y.Zhao and H.Ke (1996). Mechanistic implication of crystal structures of the cyclophilin-dipeptide complexes. Biochemistry, 35, 7362-7368. PubMed id: 8652512 DOI: 10.1021/bi960278x
Date:
27-Feb-96     Release date:   11-Jul-96    
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: 10.1021/bi960278x Biochemistry 35:7362-7368 (1996)
PubMed id: 8652512  
 
 
Mechanistic implication of crystal structures of the cyclophilin-dipeptide complexes.
Y.Zhao, H.Ke.
 
  ABSTRACT  
 
The structures of cyclophilin A complexed with dipeptides of Ser-Pro, His-Pro, and Gly-Pro have been determined and refined at high resolution. Comparison of these structures revealed that the dipeptide complexes have the same molecular conformation and the same binding of the dipeptides. The side chains of the N-terminal amino acid of the above dipeptides do not strongly interact with cyclophilin, implying their minor contribution to the cis-trans isomerization and thus accounting for the broad catalytic specificity of the enzyme. The binding of the dipeptides is similar to that of the common substrate succinyl-Ala-Ala-Pro-Phe-p-nitroanilide in terms of the N-terminal hydrogen bonding and the hydrophobic interaction of the proline side chain. However, substantial difference between these structures are observed in (1) hydrogen bonding between the carboxyl terminus of the peptides and Arg55 and between Arg55 and Gln63, (2) the side chain conformation of Arg55, and (3) water binding at the active site. These differences imply either that dipeptides are not substrates but competitive inhibitors of peptidyl-prolyl cis-trans isomerases or that dipeptides are subject to different catalytic mechanisms from tetrapeptides.
 

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.  
19761774 B.D.Janssen, and C.S.Hayes (2009).
Kinetics of paused ribosome recycling in Escherichia coli.
  J Mol Biol, 394, 251-267.  
  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.  
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.  
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
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.  
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
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
14993672 G.Kontopidis, P.Taylor, and M.D.Walkinshaw (2004).
Enzymatic and structural characterization of non-peptide ligand-cyclophilin complexes.
  Acta Crystallogr D Biol Crystallogr, 60, 479-485.
PDB codes: 1w8l 1w8m 1w8v
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.  
11180378 Wu Sy, J.Dornan, G.Kontopidis, P.Taylor, and M.D.Walkinshaw (2001).
The First Direct Determination of a Ligand Binding Constant in Protein Crystals.
  Angew Chem Int Ed Engl, 40, 582-586.
PDB code: 1e8k
11058892 M.T.Ivery (2000).
Immunophilins: switched on protein binding domains?
  Med Res Rev, 20, 452-484.  
9636134 L.Ma, L.C.Hsieh-Wilson, and P.G.Schultz (1998).
Antibody catalysis of peptidyl-prolyl cis-trans isomerization in the folding of RNase T1.
  Proc Natl Acad Sci U S A, 95, 7251-7256.  
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
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.