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PDBsum entry 2ppn

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protein links
Isomerase PDB id
2ppn
Jmol
Contents
Protein chain
107 a.a. *
Waters ×118
* Residue conservation analysis
PDB id:
2ppn
Name: Isomerase
Title: Crystal structure of fkbp12
Structure: Fk506-binding protein 1a. Chain: a. Fragment: fkbp12. Synonym: peptidyl-prolyl cis-trans isomerase, ppiase, rotamase, 12 kda fkbp, fkbp-12, immunophilin fkbp12. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: fkbp1a, fkbp1, fkbp12. Expressed in: escherichia coli. Expression_system_taxid: 562
Resolution:
0.92Å     R-factor:   0.213     R-free:   0.199
Authors: S.Szep,S.Park,G.D.Vanduyne,J.G.Saven
Key ref:
S.Szep et al. (2008). Structural coupling between FKBP12 and buried water. Proteins, 74, 603-611. PubMed id: 18704951 DOI: 10.1002/prot.22176
Date:
30-Apr-07     Release date:   27-May-08    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P62942  (FKB1A_HUMAN) -  Peptidyl-prolyl cis-trans isomerase FKBP1A
Seq:
Struc:
108 a.a.
107 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 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     membrane   7 terms 
  Biological process     chaperone-mediated protein folding   26 terms 
  Biochemical function     ion channel binding     12 terms  

 

 
    Added reference    
 
 
DOI no: 10.1002/prot.22176 Proteins 74:603-611 (2008)
PubMed id: 18704951  
 
 
Structural coupling between FKBP12 and buried water.
S.Szep, S.Park, E.T.Boder, G.D.Van Duyne, J.G.Saven.
 
  ABSTRACT  
 
Globular proteins often contain structurally well-resolved internal water molecules. Previously, we reported results from a molecular dynamics study that suggested that buried water (Wat3) may play a role in modulating the structure of the FK506 binding protein-12 (FKBP12) (Park and Saven, Proteins 2005; 60:450-463). In particular, simulations suggested that disrupting a hydrogen bond to Wat3 by mutating E60 to either A or Q would cause a structural perturbation involving the distant W59 side chain, which rotates to a new conformation in response to the mutation. This effectively remodels the ligand-binding pocket, as the side chain in the new conformation is likely to clash with bound FK506. To test whether the protein structure is in effect modulated by the binding of a buried water in the distance, we determined high-resolution (0.92-1.29 A) structures of wild-type FKBP12 and its two mutants (E60A, E60Q) by X-ray crystallography. The structures of mutant FKBP12 show that the ligand-binding pocket is indeed remodeled as predicted by the substitution at position 60, even though the water molecule does not directly interact with any of the amino acids of the binding pocket. Thus, these structures support the view that buried water molecules constitute an integral, noncovalent component of the protein structure. Additionally, this study provides an example in which predictions from molecular dynamics simulations are experimentally validated with atomic precision, thus showing that the structural features of protein-water interactions can be reliably modeled at a molecular level. Proteins 2009. (c) 2008 Wiley-Liss, Inc.
 
  Selected figure(s)  
 
Figure 3.
Figure 3. The N-terminus of the helix moves toward the center of the protein, with the main chain atoms from W59 and A60 of the mutant moving by 1.28-1.74 Å (dotted lines). (Inset) The C[ ]trace of the E60A mutant (cyan) is shown against the surface rendering of wild-type FKBP12 (purple), which is partially cut away to reveal the protein core.
Figure 5.
Figure 5. (a) FK506 (from PDB 1FKF) modeled in the ligand-binding pocket of wild-type (violet) and E60Q (cyan) FKBP12. The rotation of W59 leads to a conformation that creates steric clash between its side chain and the docked FK506. (b) The network of interacting amino acids and Wat3 in FKBP12.
 
  The above figures are reprinted by permission from John Wiley & Sons, Inc.: Proteins (2008, 74, 603-611) copyright 2008.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
19643633 J.T.Hopper, and N.J.Oldham (2009).
Collision induced unfolding of protein ions in the gas phase studied by ion mobility-mass spectrometry: the effect of ligand binding on conformational stability.
  J Am Soc Mass Spectrom, 20, 1851-1858.  
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