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PDBsum entry 1lop

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Isomerase/isomerase inhibitor PDB id
1lop
Jmol
Contents
Protein chain
164 a.a. *
Ligands
SIN-ALA-PRO-ALA-
NIT
Waters ×133
* Residue conservation analysis
PDB id:
1lop
Name: Isomerase/isomerase inhibitor
Title: Cyclophilin a complexed with succinyl-ala-pro-ala-p-nitroani
Structure: Cyclophilin a. Chain: a. Succinyl-ala-pro-ala-p-nitroanilide. Chain: b. Engineered: yes
Source: Escherichia coli. Organism_taxid: 562. Synthetic: yes
Resolution:
1.80Å     R-factor:   0.176    
Authors: M.Konno
Key ref:
M.Konno et al. (1996). The substrate-binding site in Escherichia coli cyclophilin A preferably recognizes a cis-proline isomer or a highly distorted form of the trans isomer. J Mol Biol, 256, 897-908. PubMed id: 8601841 DOI: 10.1006/jmbi.1996.0136
Date:
17-Jun-96     Release date:   23-Dec-96    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P23869  (PPIB_ECOLI) -  Peptidyl-prolyl cis-trans isomerase B
Seq:
Struc:
164 a.a.
164 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 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     cytoplasm   2 terms 
  Biological process     protein folding   2 terms 
  Biochemical function     protein binding     3 terms  

 

 
    Added reference    
 
 
DOI no: 10.1006/jmbi.1996.0136 J Mol Biol 256:897-908 (1996)
PubMed id: 8601841  
 
 
The substrate-binding site in Escherichia coli cyclophilin A preferably recognizes a cis-proline isomer or a highly distorted form of the trans isomer.
M.Konno, M.Ito, T.Hayano, N.Takahashi.
 
  ABSTRACT  
 
The three-dimensional structure of Escherichia coli cytosolic cyclophilin A (CyPA) complexed with a tripeptide (succinyl-Ala-Pro-Ala-p-nitroanilide) was refined at 1.8 A resolution by the multiple isomorphous replacement method to a crystallographic R-factor of 17.6%. As in human CyPA, the peptide binding site in E. coli enzyme is in a cleft created on the surface of the upper sheet of two orthogonal beta-sheets. In this cleft, the walls of the hydrophobic pocket are formed by the side-chains of five non-polar residues, Phe48, Met49, Phe107, Leu108, and Try120, with Phe99 at the bottom. When the cis isomer of the tripeptide binds to the enzyme, a cis-proline ring is inserted into the hydrophobic pocket. Since the binding pocket of CyPAs are largely hydrophobic, the cis isomer of a peptide can be bound more firmly than the trans isomer. Distortion of the trans isomer could lead to better binding, but at an energetic cost of the distortion energy. At the periphery of the upper beta-sheet in E. coli CyPA, conformations of loops L1, L3, and L4 and the segment connecting alpha1 and beta3 with deletions or insertions against human CyPA differ significantly from those in human CyPA. The refined model also shows that steric hindrance to attachment of cyclosporin A (CsA) prevents E. coli CyPA forming a complex with CsA. Thus, the extra amino acid residue of E. coli CyPA, polar Gln89, lies along the pathway to the hydrophobic pocket of CyPA and seems to prevent the access hydrophobic part of CsA to the cleft of CyPA.
 
  Selected figure(s)  
 
Figure 5.
Figure 5. Stereo view of superim- posed C a backbones of E. coli CyPA (red) and human CyPA (blue) (Ke, 1992). 75 C a atoms of eight b- strands, two a-helixes and one 310 helix are superimposed with an r.m.s. deviation of 0.61 Å .
Figure 8.
Figure 8. Stereo view of the cleft of E. coli CyPA. The single line represents a backbone trace. The walls of the hydrophobic pocket are formed by the side-chains of Phe48, Met49, Phe107, Leu108 and Tyr120 with Phe99 at the bottom. Side- chains of residues in the cleft: Arg43, Ile45, Phe48, Met49, Gln51, Ala86, Arg87, Thr88, G1u89, G1u97, Phe99, Phe107, Leu108 and Tyr120 are shown by ball-and-stick.
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (1996, 256, 897-908) copyright 1996.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
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.  
17103061 A.Manteca, A.I.Pelaez, R.Zardoya, and J.Sanchez (2006).
Actinobacteria cyclophilins: phylogenetic relationships and description of new class- and order-specific paralogues.
  J Mol Evol, 63, 719-732.  
16544291 K.K.Jin, S.S.Krishna, R.Schwarzenbacher, D.McMullan, P.Abdubek, S.Agarwalla, E.Ambing, H.Axelrod, J.M.Canaves, H.J.Chiu, A.M.Deacon, M.DiDonato, M.A.Elsliger, J.Feuerhelm, A.Godzik, C.Grittini, S.K.Grzechnik, J.Hale, E.Hampton, J.Haugen, M.Hornsby, L.Jaroszewski, H.E.Klock, M.W.Knuth, E.Koesema, A.Kreusch, P.Kuhn, S.A.Lesley, M.D.Miller, K.Moy, E.Nigoghossian, L.Okach, S.Oommachen, J.Paulsen, K.Quijano, R.Reyes, C.Rife, R.C.Stevens, G.Spraggon, H.van den Bedem, J.Velasquez, A.White, G.Wolf, G.W.Han, Q.Xu, K.O.Hodgson, J.Wooley, and I.A.Wilson (2006).
Crystal structure of TM1367 from Thermotoga maritima at 1.90 A resolution reveals an atypical member of the cyclophilin (peptidylprolyl isomerase) fold.
  Proteins, 63, 1112-1118.
PDB code: 1zx8
15153118 M.Guncheva, I.Ivanov, B.Galunsky, N.Stambolieva, and J.Kaneti (2004).
Kinetic studies and molecular modelling attribute a crucial role in the specificity and stereoselectivity of penicillin acylase to the pair ArgA145-ArgB263.
  Eur J Biochem, 271, 2272-2279.  
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
11080247 M.Crompton (2000).
Mitochondrial intermembrane junctional complexes and their role in cell death.
  J Physiol, 529, 11-21.  
11058892 M.T.Ivery (2000).
Immunophilins: switched on protein binding domains?
  Med Res Rev, 20, 452-484.  
10713041 U.Reidt, K.Reuter, T.Achsel, D.Ingelfinger, R.Lührmann, and R.Ficner (2000).
Crystal structure of the human U4/U6 small nuclear ribonucleoprotein particle-specific SnuCyp-20, a nuclear cyclophilin.
  J Biol Chem, 275, 7439-7442.
PDB code: 1qoi
  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
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
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.