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PDBsum entry 1zcn

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Isomerase PDB id
1zcn
Jmol
Contents
Protein chain
143 a.a. *
Ligands
PO4
1PE ×2
Waters ×110
* Residue conservation analysis
PDB id:
1zcn
Name: Isomerase
Title: Human pin1 ng mutant
Structure: Peptidyl-prolyl cis-trans isomerase nima- interacting 1. Chain: a. Synonym: rotamase pin1, ppiase pin1. Engineered: yes. Mutation: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: pin1. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Resolution:
1.90Å     R-factor:   0.226     R-free:   0.269
Authors: M.Jager,Y.Zhang,H.Nguyen,G.Dendel,M.E.Bowman,M.Gruebele, J.P.Noel,J.W.Kelly
Key ref:
M.Jäger et al. (2006). Structure-function-folding relationship in a WW domain. Proc Natl Acad Sci U S A, 103, 10648-10653. PubMed id: 16807295 DOI: 10.1073/pnas.0600511103
Date:
12-Apr-05     Release date:   20-Jun-06    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q13526  (PIN1_HUMAN) -  Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1
Seq:
Struc:
163 a.a.
143 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     midbody   5 terms 
  Biological process     metabolic process   15 terms 
  Biochemical function     protein binding     7 terms  

 

 
    Added reference    
 
 
DOI no: 10.1073/pnas.0600511103 Proc Natl Acad Sci U S A 103:10648-10653 (2006)
PubMed id: 16807295  
 
 
Structure-function-folding relationship in a WW domain.
M.Jäger, Y.Zhang, J.Bieschke, H.Nguyen, M.Dendle, M.E.Bowman, J.P.Noel, M.Gruebele, J.W.Kelly.
 
  ABSTRACT  
 
Protein folding barriers result from a combination of factors including unavoidable energetic frustration from nonnative interactions, natural variation and selection of the amino acid sequence for function, and/or selection pressure against aggregation. The rate-limiting step for human Pin1 WW domain folding is the formation of the loop 1 substructure. The native conformation of this six-residue loop positions side chains that are important for mediating protein-protein interactions through the binding of Pro-rich sequences. Replacement of the wild-type loop 1 primary structure by shorter sequences with a high propensity to fold into a type-I' beta-turn conformation or the statistically preferred type-I G1 bulge conformation accelerates WW domain folding by almost an order of magnitude and increases thermodynamic stability. However, loop engineering to optimize folding energetics has a significant downside: it effectively eliminates WW domain function according to ligand-binding studies. The energetic contribution of loop 1 to ligand binding appears to have evolved at the expense of fast folding and additional protein stability. Thus, the two-state barrier exhibited by the wild-type human Pin1 WW domain principally results from functional requirements, rather than from physical constraints inherent to even the most efficient loop formation process.
 
  Selected figure(s)  
 
Figure 1.
Fig. 1. Loop structures and sequences of WW domains. (a) Backbone diagram of the loop 1 substructure in WT Pin WW (residues S16–R21) [Protein Data Bank (PDB) ID code 1PIN]. (b) Backbone diagram of the loop 1 substructure in WT FBP WW (residues T13–K17) (PDB ID code 1E01). Backbone H-bonds are indicated by black dotted lines. (c) Aligned sequences of the WT Pin WW domain (variant 1) and loop 1 redesigned variants 2–9 and the redesigned and sequence-minimized FBP WW variants (10 and 11). -strand residues are colored blue, residues that were mutated or deleted upon loop 1 redesign are in red, and all other residues are in gray.
Figure 3.
Fig. 3. Effect of loop 1 redesign on WW domain stability. (a) Normalized equilibrium unfolding transitions for Pin WW (variant 1) and variants 2–6 with either a confirmed (2) or predicted (3–6) (3:5) type-I bulge turn. (b) Normalized equilibrium unfolding transitions for variants 1 and 7–9 with either a confirmed (7) or predicted (8, 9) (2:2) type-I' -hairpin turn. (c) Normalized equilibrium unfolding transitions for FBP (WW variant 10) with a confirmed (3:5) type-I G1 bulge turn and variant 11 with a predicted (4:6) loop.
 
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21402934 E.L.Baxter, P.A.Jennings, and J.N.Onuchic (2011).
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21548671 J.H.Prinz, H.Wu, M.Sarich, B.Keller, M.Senne, M.Held, J.D.Chodera, C.Schütte, and F.Noé (2011).
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20574990 K.Hong Lim, C.K.Hsu, and S.Park (2010).
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PDB code: 2kbu
19491935 A.I.Bartlett, and S.E.Radford (2009).
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19887634 F.Noé, C.Schütte, E.Vanden-Eijnden, L.Reich, and T.R.Weikl (2009).
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19626709 H.Fu, G.R.Grimsley, A.Razvi, J.M.Scholtz, and C.N.Pace (2009).
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19413983 P.L.Freddolino, S.Park, B.Roux, and K.Schulten (2009).
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19792076 P.Metzner, F.Noé, and C.Schütte (2009).
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18275088 A.M.Marcelino, and L.M.Gierasch (2008).
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18601313 F.Noé (2008).
Probability distributions of molecular observables computed from Markov models.
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18378442 F.Noé, and S.Fischer (2008).
Transition networks for modeling the kinetics of conformational change in macromolecules.
  Curr Opin Struct Biol, 18, 154-162.  
18844292 M.Jager, S.Deechongkit, E.K.Koepf, H.Nguyen, J.Gao, E.T.Powers, M.Gruebele, and J.W.Kelly (2008).
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  Biopolymers, 90, 751-758.  
18200608 O.Okhrimenko, and I.Jelesarov (2008).
A survey of the year 2006 literature on applications of isothermal titration calorimetry.
  J Mol Recognit, 21, 1.  
18339748 P.L.Freddolino, F.Liu, M.Gruebele, and K.Schulten (2008).
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18708465 R.D.Hills, and C.L.Brooks (2008).
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17239580 D.J.Brockwell, and S.E.Radford (2007).
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17766376 M.Jäger, M.Dendle, A.A.Fuller, and J.W.Kelly (2007).
A cross-strand Trp Trp pair stabilizes the hPin1 WW domain at the expense of function.
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17334375 T.Peng, J.S.Zintsmaster, A.T.Namanja, and J.W.Peng (2007).
Sequence-specific dynamics modulate recognition specificity in WW domains.
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17766370 T.Sharpe, A.L.Jonsson, T.J.Rutherford, V.Daggett, and A.R.Fersht (2007).
The role of the turn in beta-hairpin formation during WW domain folding.
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16855578 J.W.Kelly (2006).
Structural biology: proteins downhill all the way.
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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.