PDBsum entry 2kbu

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protein links
Isomerase PDB id
Protein chain
31 a.a. *
* Residue conservation analysis
PDB id:
Name: Isomerase
Title: Nmr solution structure of pin1 ww domain mutant with beta turn mimic at position 12
Structure: Peptidyl-prolyl cis-trans isomerase nima- interacting 1. Chain: a. Fragment: unp residues 6-39. Synonym: rotamase pin1, ppiase pin1. Engineered: yes. Mutation: yes. Other_details: residues rssg replaced by the beta-turn mimic cfd
Source: Synthetic: yes. Other_details: residues rssg replaced by the beta-turn mimic cfd
NMR struc: 15 models
Authors: A.A.Fuller,G.Bhabha,D.A.Case
Key ref:
A.A.Fuller et al. (2009). Evaluating beta-turn mimics as beta-sheet folding nucleators. Proc Natl Acad Sci U S A, 106, 11067-11072. PubMed id: 19541614 DOI: 10.1073/pnas.0813012106
08-Dec-08     Release date:   07-Jul-09    
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Protein chain
Pfam   ArchSchema ?
Q13526  (PIN1_HUMAN) -  Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1
163 a.a.
31 a.a.*
Key:    PfamA domain  Secondary structure
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 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


    Added reference    
DOI no: 10.1073/pnas.0813012106 Proc Natl Acad Sci U S A 106:11067-11072 (2009)
PubMed id: 19541614  
Evaluating beta-turn mimics as beta-sheet folding nucleators.
A.A.Fuller, D.Du, F.Liu, J.E.Davoren, G.Bhabha, G.Kroon, D.A.Case, H.J.Dyson, E.T.Powers, P.Wipf, M.Gruebele, J.W.Kelly.
Beta-turns are common conformations that enable proteins to adopt globular structures, and their formation is often rate limiting for folding. Beta-turn mimics, molecules that replace the i + 1 and i + 2 amino acid residues of a beta-turn, are envisioned to act as folding nucleators by preorganizing the pendant polypeptide chains, thereby lowering the activation barrier for beta-sheet formation. However, the crucial kinetic experiments to demonstrate that beta-turn mimics can act as strong nucleators in the context of a cooperatively folding protein have not been reported. We have incorporated 6 beta-turn mimics simulating varied beta-turn types in place of 2 residues in an engineered beta-turn 1 or beta-bulge turn 1 of the Pin 1 WW domain, a three-stranded beta-sheet protein. We present 2 lines of kinetic evidence that the inclusion of beta-turn mimics alters beta-sheet folding rates, enabling us to classify beta-turn mimics into 3 categories: those that are weak nucleators but permit Pin WW folding, native-like nucleators, and strong nucleators. Strong nucleators accelerate folding relative to WW domains incorporating all alpha-amino acid sequences. A solution NMR structure reveals that the native Pin WW beta-sheet structure is retained upon incorporating a strong E-olefin nucleator. These beta-turn mimics can now be used to interrogate protein folding transition state structures and the 2 kinetic analyses presented can be used to assess the nucleation capacity of other beta-turn mimics.
  Selected figure(s)  
Figure 1.
β-Turn mimics studied.
Figure 2.
Comparison of the solution structures of the Pin1 WW domain. (A) Superposition of 12 structures of the WT protein (36; PDB ID code 2kcf) (B) Superposition of 15 structures of variant C-4 (PDB ID code 2kbu). (C) Superposition of a low-energy structure from each of the ensembles in (A) and (B). The inset shows the structure of dipeptide replacement 4 in loop 1.
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20937907 B.Eckhardt, W.Grosse, L.O.Essen, and A.Geyer (2010).
Structural characterization of a beta-turn mimic within a protein-protein interface.
  Proc Natl Acad Sci U S A, 107, 18336-18341.
PDB codes: 2ww6 2ww7
20673368 P.Kountouris, and J.D.Hirst (2010).
Predicting beta-turns and their types using predicted backbone dihedral angles and secondary structures.
  BMC Bioinformatics, 11, 407.  
  20725595 P.Wipf, J.Xiao, and C.R.Stephenson (2009).
Peptide-Like Molecules (PLMs): A Journey from Peptide Bond Isosteres to Gramicidin S Mimetics and Mitochondrial Targeting Agents.
  Chimia (Aarau), 63, 764-775.  
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