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PDBsum entry 3k0p

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protein links
Isomerase PDB id
3k0p
Jmol
Contents
Protein chain
162 a.a. *
Waters ×218
* Residue conservation analysis
PDB id:
3k0p
Name: Isomerase
Title: Cryogenic structure of cypa mutant ser99thr
Structure: Cyclophilin a. Chain: a. Synonym: peptidyl-prolyl cis-trans isomerase a, ppiase a, r cyclosporin a-binding protein. Engineered: yes. Mutation: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: ppia, cypa. Expressed in: escherichia coli. Expression_system_taxid: 562
Resolution:
1.65Å     R-factor:   0.150     R-free:   0.176
Authors: J.S.Fraser,T.Alber
Key ref: J.S.Fraser et al. (2009). Hidden alternative structures of proline isomerase essential for catalysis. Nature, 462, 669-673. PubMed id: 19956261
Date:
24-Sep-09     Release date:   08-Dec-09    
PROCHECK
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 Headers
 References

Protein chain
Pfam   ArchSchema ?
P62937  (PPIA_HUMAN) -  Peptidyl-prolyl cis-trans isomerase A
Seq:
Struc:
165 a.a.
162 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     extracellular region   5 terms 
  Biological process     viral reproduction   18 terms 
  Biochemical function     protein binding     7 terms  

 

 
    Added reference    
 
 
Nature 462:669-673 (2009)
PubMed id: 19956261  
 
 
Hidden alternative structures of proline isomerase essential for catalysis.
J.S.Fraser, M.W.Clarkson, S.C.Degnan, R.Erion, D.Kern, T.Alber.
 
  ABSTRACT  
 
A long-standing challenge is to understand at the atomic level how protein dynamics contribute to enzyme catalysis. X-ray crystallography can provide snapshots of conformational substates sampled during enzymatic reactions, while NMR relaxation methods reveal the rates of interconversion between substates and the corresponding relative populations. However, these current methods cannot simultaneously reveal the detailed atomic structures of the rare states and rationalize the finding that intrinsic motions in the free enzyme occur on a timescale similar to the catalytic turnover rate. Here we introduce dual strategies of ambient-temperature X-ray crystallographic data collection and automated electron-density sampling to structurally unravel interconverting substates of the human proline isomerase, cyclophilin A (CYPA, also known as PPIA). A conservative mutation outside the active site was designed to stabilize features of the previously hidden minor conformation. This mutation not only inverts the equilibrium between the substates, but also causes large, parallel reductions in the conformational interconversion rates and the catalytic rate. These studies introduce crystallographic approaches to define functional minor protein conformations and, in combination with NMR analysis of the enzyme dynamics in solution, show how collective motions directly contribute to the catalytic power of an enzyme.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
  23201676 Y.Ye, G.Blaser, M.H.Horrocks, M.J.Ruedas-Rama, S.Ibrahim, A.A.Zhukov, A.Orte, D.Klenerman, S.E.Jackson, and D.Komander (2012).
Ubiquitin chain conformation regulates recognition and activity of interacting proteins.
  Nature, 492, 266-270.  
  21317893 A.Shen, P.J.Lupardus, M.M.Gersch, A.W.Puri, V.E.Albrow, K.C.Garcia, and M.Bogyo (2011).
Defining an allosteric circuit in the cysteine protease domain of Clostridium difficile toxins.
  Nat Struct Mol Biol, 18, 364-371.
PDB code: 3pee
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.