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PDBsum entry 1cyh
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Isomerase(peptidyl-prolyl cis-trans) PDB id
1cyh

 

 

 

 

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Contents
Protein chain
164 a.a.
Ligands
ALA-PRO
Waters ×240
Superseded by: 2cyh
PDB id:
1cyh
Name: Isomerase(peptidyl-prolyl cis-trans)
Title: Crystal structure of cyclophilin a complexed with substrate ala-pro suggests a solvent-assisted mechanism of cis- trans isomerization
Structure: Chain: a. Engineered: yes. Chain: b. Engineered: yes
Source: not given
Resolution:
1.64Å     R-factor:   0.196    
Authors: H.Ke,D.Mayrose,W.Cao
Key ref: H.Ke et al. (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. PubMed id: 8475075 DOI: 10.1073/pnas.90.8.3324
Date:
14-Dec-92     Release date:   30-Apr-94    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
No UniProt id for this chain
Struc: 164 a.a.
Key:    Secondary structure  CATH domain

 

 
DOI no: 10.1073/pnas.90.8.3324 Proc Natl Acad Sci U S A 90:3324-3328 (1993)
PubMed id: 8475075  
 
 
Crystal structure of cyclophilin A complexed with substrate Ala-Pro suggests a solvent-assisted mechanism of cis-trans isomerization.
H.Ke, D.Mayrose, W.Cao.
 
  ABSTRACT  
 
Cyclophilin is a binding protein for the immunosuppressive drug cyclosporin A and is also an enzyme with peptidyl-prolyl cis-trans isomerase activity. The crystal structure of cyclophilin A complexed with the substrate Ala-Pro has been determined and refined to an R factor of 0.196 at 1.64-A resolution. The structure shows that only the cis form of Ala-Pro binds cyclophilin A despite the fact that Ala-Pro has an equilibrium majority of the trans form in solution. Simulation of the cis-trans isomerization in an ESV10 graphics system suggests a solvent-assisted mechanism in which first the peptidyl-prolyl bond is desolvated at the ground state by binding to the hydrophobic pocket of the active site, and later the intermediate state is stabilized by a hydrogen bond between the carbonyl oxygen of the amide bond and a bound water molecule.
 

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
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.  
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.  
18029417 T.Ikura, and N.Ito (2007).
Requirements for peptidyl-prolyl isomerization activity: a comprehensive mutational analysis of the substrate-binding cavity of FK506-binding protein 12.
  Protein Sci, 16, 2618-2625.  
  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.  
16302169 X.J.Wang, and F.A.Etzkorn (2006).
Peptidyl-prolyl isomerase inhibitors.
  Biopolymers, 84, 125-146.  
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
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
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
10602736 M.C.Cruz, M.Del Poeta, P.Wang, R.Wenger, G.Zenke, V.F.Quesniaux, N.R.Movva, J.R.Perfect, M.E.Cardenas, and J.Heitman (2000).
Immunosuppressive and nonimmunosuppressive cyclosporine analogs are toxic to the opportunistic fungal pathogen Cryptococcus neoformans via cyclophilin-dependent inhibition of calcineurin.
  Antimicrob Agents Chemother, 44, 143-149.  
  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
  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.  
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
9101762 P.Taylor, V.Mikol, J.Kallen, P.Burkhard, and M.D.Walkinshaw (1996).
Conformational polymorphism in peptidic and nonpeptidic drug molecules.
  Biopolymers, 40, 585-592.  
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
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
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
8341703 J.Friedman, M.Trahey, and I.Weissman (1993).
Cloning and characterization of cyclophilin C-associated protein: a candidate natural cellular ligand for cyclophilin C.
  Proc Natl Acad Sci U S A, 90, 6815-6819.  
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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