spacer
spacer

PDBsum entry 2x2d

Go to PDB code: 
protein Protein-protein interface(s) links
Isomerase/viral protein PDB id
2x2d
Jmol
Contents
Protein chains
165 a.a. *
146 a.a. *
136 a.a. *
Waters ×208
* Residue conservation analysis
PDB id:
2x2d
Name: Isomerase/viral protein
Title: Acetyl-cypa:hiv-1 n-term capsid domain complex
Structure: Peptidyl-prolyl cis-trans isomerase a. Chain: c, b. Synonym: ppiase a, rotamase a, cyclophilin a, cyclosporin a protein, cypa. Engineered: yes. Capsid protein p24. Chain: d, e. Fragment: residues 133-278. Synonym: ca, gag polyprotein
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562. Human immunodeficiency virus 1. Organism_taxid: 11676
Resolution:
1.90Å     R-factor:   0.199     R-free:   0.256
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.*
Protein chain
Pfam   ArchSchema ?
P12497  (POL_HV1N5) -  Gag-Pol polyprotein
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
1435 a.a.
146 a.a.
Protein chain
Pfam   ArchSchema ?
P12497  (POL_HV1N5) -  Gag-Pol polyprotein
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
1435 a.a.
136 a.a.
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class 1: Chains B, C: 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)
   Enzyme class 2: Chains D, E: E.C.2.7.7.49  - RNA-directed Dna polymerase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Deoxynucleoside triphosphate + DNA(n) = diphosphate + DNA(n+1)
Deoxynucleoside triphosphate
+ DNA(n)
= diphosphate
+ DNA(n+1)
   Enzyme class 3: Chains D, E: E.C.2.7.7.7  - DNA-directed Dna polymerase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Deoxynucleoside triphosphate + DNA(n) = diphosphate + DNA(n+1)
Deoxynucleoside triphosphate
+ DNA(n)
= diphosphate
+ DNA(n+1)
   Enzyme class 4: Chains D, E: E.C.3.1.13.2  - Exoribonuclease H.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Exonucleolytic cleavage to 5'-phosphomonoester oligonucleotides in both 5'- to 3'- and 3'- to 5'-directions.
   Enzyme class 5: Chains D, E: E.C.3.1.26.13  - Retroviral ribonuclease H.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
   Enzyme class 6: Chains D, E: E.C.3.4.23.16  - HIV-1 retropepsin.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Specific for a P1 residue that is hydrophobic, and P1' variable, but often Pro.
Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   7 terms 
  Biological process     viral reproduction   18 terms 
  Biochemical function     protein binding     7 terms  

 

 
    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.