PDBsum entry 1w8v

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protein links
Isomerase PDB id
Protein chain
165 a.a. *
Waters ×192
* Residue conservation analysis
PDB id:
Name: Isomerase
Title: Enzymatic and structural characterization of non peptide ligand cyclophilin complexes
Structure: Peptidyl-prolyl cis-trans isomerase a. Chain: a. Synonym: cyclophilin a, ppiase, rotamase. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606
1.7Å     R-factor:   0.174     R-free:   0.219
Authors: G.Kontopidis,P.Taylor,M.Walkinshaw
Key ref:
G.Kontopidis et al. (2004). Enzymatic and structural characterization of non-peptide ligand-cyclophilin complexes. Acta Crystallogr D Biol Crystallogr, 60, 479-485. PubMed id: 14993672 DOI: 10.1107/S0907444904000174
28-Sep-04     Release date:   30-Sep-04    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P62937  (PPIA_HUMAN) -  Peptidyl-prolyl cis-trans isomerase A
165 a.a.
165 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - 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: 10.1107/S0907444904000174 Acta Crystallogr D Biol Crystallogr 60:479-485 (2004)
PubMed id: 14993672  
Enzymatic and structural characterization of non-peptide ligand-cyclophilin complexes.
G.Kontopidis, P.Taylor, M.D.Walkinshaw.
Piperidine ligands are described that provide the first examples of non-peptidic ligand structures for the cyclophilin family of proteins. Crystal structures of two ligand complexes are compared with the unliganded protein and show ligand-induced changes in side-chain conformation and water binding. A peptidylprolyl cis-trans-isomerase assay showed the dissociation constants of the two ligands to be 320 and 25 mM. This study also provides the first published data for both enzymatic activity and three-dimensional structure for any protein-ligand complex that binds with a high-millimolar dissociation constant. The structures may be of relevance in the field of drug design, as they suggest starting points for the design of larger tighter-binding analogues.
  Selected figure(s)  
Figure 3.
Figure 3 (a) Overlay of native hCypA (cyan) with hCypA-ACMPIP (atom-type colours). Close contacts between the ACMPIP ligand with surrounding atoms are shown. ACMPIP makes one hydrogen bond to Asn102 N (2.8 ). The most hydrophobic part of the ACMPIP molecule (the methylpiperidine ring) fits into the hydrophobic pocket. van der Waals contacts are made from the ligand to the side chains of six amino acids (Arg55, Phe 60, Met61, Gln63, Phe113 and His126). (b) Overlay of native hCypA (cyan) with the hCypA-ETPIPG in both binding modes (ALT2, green; ALT1, purple). The main difference between the native protein structure and the structure with ETPIPG in the binding site is the movement of the side chain of Met61. The overall backbone conformations of the three structures are very similar. An r.m.s. fit of all protein atoms except residues 1-4, 67-76 and 162-165 between native and the ACMPIP complex is 0.286 and that between the ACMPIP and ETPIPG complexes is 0.367 .
Figure 5.
Figure 5 Diagrammatic representation of the major ligand-protein interactions. Hydrogen bonds are shown as dotted lines. The hydrophobic pocket is primarily bounded by the side chains of Phe113 and Phe60, which are shown as green ovals.
  The above figures are reprinted by permission from the IUCr: Acta Crystallogr D Biol Crystallogr (2004, 60, 479-485) copyright 2004.  
  Figures were selected by an automated process.