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PDBsum entry 2biu

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Isomerase PDB id
2biu
Jmol
Contents
Protein chain
164 a.a. *
Ligands
DMS ×4
Waters ×340
* Residue conservation analysis
PDB id:
2biu
Name: Isomerase
Title: Crystal structure of human cyclophilin d at 1.7 a resolution, dmso complex
Structure: Peptidyl-prolyl cis-trans isomerase. Chain: x. Fragment: residues 43-207. Synonym: cyclophilin f, ppiase, rotamase, cyclophilin d. Engineered: yes. Mutation: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
1.71Å     R-factor:   0.150     R-free:   0.185
Authors: M.Hennig,R.Thoma,M.Stihle,D.Schlatter
Key ref:
D.Schlatter et al. (2005). Crystal engineering yields crystals of cyclophilin D diffracting to 1.7 A resolution. Acta Crystallogr D Biol Crystallogr, 61, 513-519. PubMed id: 15858260 DOI: 10.1107/S0907444905003070
Date:
26-Jan-05     Release date:   26-Jan-05    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P30405  (PPIF_HUMAN) -  Peptidyl-prolyl cis-trans isomerase F, mitochondrial
Seq:
Struc:
207 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!
  Biological process     protein folding   2 terms 
  Biochemical function     peptidyl-prolyl cis-trans isomerase activity     1 term  

 

 
    Added reference    
 
 
DOI no: 10.1107/S0907444905003070 Acta Crystallogr D Biol Crystallogr 61:513-519 (2005)
PubMed id: 15858260  
 
 
Crystal engineering yields crystals of cyclophilin D diffracting to 1.7 A resolution.
D.Schlatter, R.Thoma, E.Küng, M.Stihle, F.Müller, E.Borroni, A.Cesura, M.Hennig.
 
  ABSTRACT  
 
In the pharmaceutical industry, knowledge of the three-dimensional structure of a specific target facilitates the drug-discovery process. Despite possessing favoured analytical properties such as high purity and monodispersion in light scattering, some proteins are not capable of forming crystals suitable for X-ray analysis. Cyclophilin D, an isoform of cyclophilin that is expressed in the mitochondria, was selected as a drug target for the treatment of cardiac disorders. As the wild-type enzyme defied all attempts at crystallization, protein engineering on the enzyme surface was performed. The K133I mutant gave crystals that diffracted to 1.7 A resolution using in-house X-ray facilities and were suitable for soaking experiments. The crystals were very robust and diffraction was maintained after soaking in 25% DMSO solution: excellent conditions for the rapid analysis of complex structures including crystallographic fragment screening.
 
  Selected figure(s)  
 
Figure 5.
Figure 5 (a) Stereoview in ball-and-stick representation with sticks coloured blue and yellow for the molecules that form the crystal contact. The mutation K133I favors the formation of the crystal contact with mainly hydrophobic interactions. A lysine side chain at this position would cause steric clashes and disable this crystal packing.
Figure 6.
Figure 6 Soaking with 25% DMSO resulted in four DMSO-binding sites with very high confidence. Two DMSO molecules were identified in close proximity to the active site of the enzyme. DMSO-1 forms a hydrogen bond to the guanidine group of Arg55 and DMSO-2 forms a hydrogen bond to Asn102 NH, a hydrogen bond that is also formed in the complex of cyclophilin A with cyclosporin A.
 
  The above figures are reprinted by permission from the IUCr: Acta Crystallogr D Biol Crystallogr (2005, 61, 513-519) copyright 2005.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20175748 K.E.Muirhead, E.Borger, L.Aitken, S.J.Conway, and F.J.Gunn-Moore (2010).
The consequences of mitochondrial amyloid beta-peptide in Alzheimer's disease.
  Biochem J, 426, 255-270.  
20614016 W.L.Yau, T.Blisnick, J.F.Taly, M.Helmer-Citterich, C.Schiene-Fischer, O.Leclercq, J.Li, D.Schmidt-Arras, M.A.Morales, C.Notredame, D.Romo, P.Bastin, and G.F.Späth (2010).
Cyclosporin A treatment of Leishmania donovani reveals stage-specific functions of cyclophilins in parasite proliferation and viability.
  PLoS Negl Trop Dis, 4, e729.  
18076075 K.Kajitani, M.Fujihashi, Y.Kobayashi, S.Shimizu, Y.Tsujimoto, and K.Miki (2008).
Crystal structure of human cyclophilin D in complex with its inhibitor, cyclosporin A at 0.96-A resolution.
  Proteins, 70, 1635-1639.
PDB code: 2z6w
  18931446 M.Senda, S.Muto, M.Horikoshi, and T.Senda (2008).
Effect of leucine-to-methionine substitutions on the diffraction quality of histone chaperone SET/TAF-Ibeta/INHAT crystals.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 64, 960-965.  
  18084085 B.Liu, V.M.Luna, Y.Chen, C.D.Stout, and J.A.Fee (2007).
An unexpected outcome of surface engineering an integral membrane protein: improved crystallization of cytochrome ba(3) from Thermus thermophilus.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 63, 1029-1034.
PDB codes: 2qpd 2qpe
17453156 S.Grimm, and D.Brdiczka (2007).
The permeability transition pore in cell death.
  Apoptosis, 12, 841-855.  
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.