PDBsum entry 2dg4

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protein ligands links
Isomerase PDB id
Jmol PyMol
Protein chain
107 a.a. *
Waters ×153
* Residue conservation analysis
PDB id:
Name: Isomerase
Title: Fk506-binding protein mutant wf59 complexed with rapamycin
Structure: Fk506-binding protein 1a. Chain: a. Synonym: peptidyl-prolyl cis-trans isomerase, ppiase, rotam kda fkbp, fkbp-12, immunophilin fkbp12. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693.
1.70Å     R-factor:   0.196     R-free:   0.213
Authors: A.M.Buckle
Key ref:
K.F.Fulton et al. (2003). Energetic and structural analysis of the role of tryptophan 59 in FKBP12. Biochemistry, 42, 2364-2372. PubMed id: 12600203 DOI: 10.1021/bi020564a
08-Mar-06     Release date:   25-Apr-06    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P62942  (FKB1A_HUMAN) -  Peptidyl-prolyl cis-trans isomerase FKBP1A
108 a.a.
107 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.  - 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   6 terms 
  Biological process     chaperone-mediated protein folding   26 terms 
  Biochemical function     ion channel binding     12 terms  


    Added reference    
DOI no: 10.1021/bi020564a Biochemistry 42:2364-2372 (2003)
PubMed id: 12600203  
Energetic and structural analysis of the role of tryptophan 59 in FKBP12.
K.F.Fulton, S.E.Jackson, A.M.Buckle.
Tryptophan 59 forms the seat of the hydrophobic ligand-binding site in the small immunophilin FKBP12. Mutating this residue to phenylalanine or leucine stabilizes the protein by 2.72 and 2.35 kcal mol(-1), respectively. Here we report the stability data and 1.7 A resolution crystal structures of both mutant proteins, complexed with the immunosuppressant rapamycin. Both structures show a relatively large response to mutation involving a helical bulge at the mutation site and the loss of a hydrogen bond that anchors a nearby loop. The increased stability of the mutants is probably due to a combination of improved packing and an entropic gain at the mutation site. The structures are almost identical to that of wild-type FKBP12.6, an isoform of FKBP12 that differs by 18 residues, including Trp59, in its sequence. Therefore, the structural difference between the two isoforms can be attributed almost entirely to the identity of residue 59. It is likely that in FKBP12-ligand complexes Trp59 provides added binding energy at the active site at the expense of protein stability, a characteristic common to other proteins. FKBP12 associates with the ryanodine receptor in skeletal muscle (RyR1), while FKBP12.6 selectively binds the ryanodine receptor in cardiac muscle (RyR2). The structural response to mutation suggests that residue 59 contributes to the specificity of binding between FKBP12 isoforms and ryanodine receptors.

Literature references that cite this PDB file's key reference

  PubMed id Reference
21287615 E.H.Kellogg, A.Leaver-Fay, and D.Baker (2011).
Role of conformational sampling in computing mutation-induced changes in protein structure and stability.
  Proteins, 79, 830-838.  
18073107 S.Yin, F.Ding, and N.V.Dokholyan (2007).
Modeling backbone flexibility improves protein stability estimation.
  Structure, 15, 1567-1576.  
18029417 T.Ikura, and N.Ito (2007).
Requirements for peptidyl-prolyl isomerization activity: a comprehensive mutational analysis of the substrate-binding cavity of FK506-binding protein 12.
  Protein Sci, 16, 2618-2625.  
15937899 S.Park, and J.G.Saven (2005).
Statistical and molecular dynamics studies of buried waters in globular proteins.
  Proteins, 60, 450-463.  
15033987 E.H.Lee, S.H.Rho, S.J.Kwon, S.H.Eom, P.D.Allen, and d.o. .H.Kim (2004).
N-terminal region of FKBP12 is essential for binding to the skeletal ryanodine receptor.
  J Biol Chem, 279, 26481-26488.  
12813039 B.Campanini, S.Raboni, S.Vaccari, L.Zhang, P.F.Cook, T.L.Hazlett, A.Mozzarelli, and S.Bettati (2003).
Surface-exposed tryptophan residues are essential for O-acetylserine sulfhydrylase structure, function, and stability.
  J Biol Chem, 278, 37511-37519.  
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