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PDBsum entry 2x2a

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protein ligands Protein-protein interface(s) links
Isomerase PDB id
2x2a
Jmol
Contents
Protein chains
165 a.a. *
Ligands
GOL
SO4 ×2
Waters ×586
* Residue conservation analysis
PDB id:
2x2a
Name: Isomerase
Title: Free acetyl-cypa trigonal form
Structure: Peptidyl-prolyl cis-trans isomerase a. Chain: a, b. Synonym: ppiase a, rotamase a, cyclophilin a, cyclosporin a-binding protein, cypa. Ec: 5.2.1.8
Source: Homo sapiens. Human. Organism_taxid: 9606
Resolution:
1.40Å     R-factor:   0.125     R-free:   0.161
Authors: M.Lammers,H.Neumann,J.W.Chin,L.C.James
Key ref: M.Lammers et al. (2010). Acetylation regulates cyclophilin A catalysis, immunosuppression and HIV isomerization. Nat Chem Biol, 6, 331-337. PubMed id: 20364129
Date:
12-Jan-10     Release date:   23-Mar-10    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P62937  (PPIA_HUMAN) -  Peptidyl-prolyl cis-trans isomerase A
Seq:
Struc:
165 a.a.
165 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 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    
 
 
Nat Chem Biol 6:331-337 (2010)
PubMed id: 20364129  
 
 
Acetylation regulates cyclophilin A catalysis, immunosuppression and HIV isomerization.
M.Lammers, H.Neumann, J.W.Chin, L.C.James.
 
  ABSTRACT  
 
Cyclophilin A (CypA) is a ubiquitous cis-trans prolyl isomerase with key roles in immunity and viral infection. CypA suppresses T-cell activation through cyclosporine complexation and is required for effective HIV-1 replication in host cells. We show that CypA is acetylated in diverse human cell lines and use a synthetically evolved acetyllysyl-tRNA synthetase/tRNA(CUA) pair to produce recombinant acetylated CypA in Escherichia coli. We determined atomic-resolution structures of acetylated CypA and its complexes with cyclosporine and HIV-1 capsid. Acetylation markedly inhibited CypA catalysis of cis to trans isomerization and stabilized cis rather than trans forms of the HIV-1 capsid. Furthermore, CypA acetylation antagonized the immunosuppressive effects of cyclosporine by inhibiting the sequential steps of cyclosporine binding and calcineurin inhibition. Our results reveal that acetylation regulates key functions of CypA in immunity and viral infection and provide a general set of mechanisms by which acetylation modulates interactions to regulate cell function.