PDBsum entry 1k5r

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protein ligands links
Signaling protein PDB id
Protein chain
41 a.a. *
* Residue conservation analysis
PDB id:
Name: Signaling protein
Title: Yap65 ww domain s24-amino-ethylsulfanyl-acetic acid mutant
Structure: 65 kda yes-associated protein. Chain: a. Fragment: ww domain, residues 5-44. Synonym: yap65. Yes-associated protein 65 kda. Engineered: yes. Mutation: yes. Other_details: 40-peptide construct with synthetic amino- ethyl-sulfanyl-acetic acid link at position 24. Fragment of wbp-1.
Source: Synthetic: yes. Other_details: the sequence occurs naturally in humans. Other_details: the sequence occurs naturally in humans
NMR struc: 10 models
Authors: N.Ferguson,J.R.Pires,F.Toepert,C.M.Johnson,Y.P.Pan, R.Volkmer-Engert,J.Schneider-Mergener,V.Daggett,H.Oschkinat A.R.Fersht
Key ref:
N.Ferguson et al. (2001). Using flexible loop mimetics to extend phi-value analysis to secondary structure interactions. Proc Natl Acad Sci U S A, 98, 13008-13013. PubMed id: 11687614 DOI: 10.1073/pnas.221467398
12-Oct-01     Release date:   02-Nov-01    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P46937  (YAP1_HUMAN) -  Yorkie homolog
504 a.a.
41 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)


DOI no: 10.1073/pnas.221467398 Proc Natl Acad Sci U S A 98:13008-13013 (2001)
PubMed id: 11687614  
Using flexible loop mimetics to extend phi-value analysis to secondary structure interactions.
N.Ferguson, J.R.Pires, F.Toepert, C.M.Johnson, Y.P.Pan, R.Volkmer-Engert, J.Schneider-Mergener, V.Daggett, H.Oschkinat, A.Fersht.
Chemical synthesis allows the incorporation of nonnatural amino acids into proteins that may provide previously untried probes of their folding pathway and thermodynamic stability. We have used a flexible thioether linker as a loop mimetic in the human yes kinase-associated protein (YAP 65) WW domain, a three-stranded, 44-residue, beta-sheet protein. This linkage avoids problems of incorporating sequences that constrain loops to the extent that they significantly change the nature of the denatured state with concomitant effects on the folding kinetics. An NMR solution structure shows that the thioether linker had little effect on the global fold of the domain, although the loop is apparently more dynamic. The thioether variants are destabilized by up to 1.4 kcal/mol (1 cal = 4.18 J). Preliminary Phi-value analysis showed that the first loop is highly structured in the folding transition state, and the second loop is essentially unstructured. These data are consistent with results from simulated unfolding and detailed protein-engineering studies of structurally homologous WW domains. Previously, Phi-value analysis was limited to studying side-chain interactions. The linkers used here extend the protein engineering method directly to secondary-structure interactions.
  Selected figure(s)  
Figure 1.
Fig. 1. Amino acid sequence of the YAP 65 WW domain and its thioether analogues S24, S24G25 and I33. In the sequences, Z refers to the nonnatural amino acid (2-amino-ethylsulfanyl)-acetic acid.
Figure 6.
Fig. 6. Thermal unfolding simulations of the FBP28 WW domain. The -strands are colored as follows: 1 (residues 8-12), red; 2 (res. 18-22), green; and 3 (res. 27-30), blue. This figure was made by using MIDASPLUS (38). The transition states for unfolding are near 2 ns.
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
  21365688 J.Xu, L.Huang, and E.I.Shakhnovich (2011).
The ensemble folding kinetics of the FBP28 WW domain revealed by an all-atom Monte Carlo simulation in a knowledge-based potential.
  Proteins, 79, 1704-1714.  
20159161 J.Juraszek, and P.G.Bolhuis (2010).
(Un)Folding mechanisms of the FBP28 WW domain in explicit solvent revealed by multiple rare event simulation methods.
  Biophys J, 98, 646-656.  
19948125 A.L.Jonsson, K.A.Scott, and V.Daggett (2009).
Dynameomics: a consensus view of the protein unfolding/folding transition state ensemble across a diverse set of protein folds.
  Biophys J, 97, 2958-2966.  
19525973 J.Gao, D.A.Bosco, E.T.Powers, and J.W.Kelly (2009).
Localized thermodynamic coupling between hydrogen bonding and microenvironment polarity substantially stabilizes proteins.
  Nat Struct Mol Biol, 16, 684-690.  
19299503 K.Sato, C.Li, I.Salard, A.J.Thompson, M.J.Banfield, and C.Dennison (2009).
Metal-binding loop length and not sequence dictates structure.
  Proc Natl Acad Sci U S A, 106, 5616-5621.
PDB codes: 3fs9 3fsa 3fsv 3fsw 3fsz 3ft0
18844292 M.Jager, S.Deechongkit, E.K.Koepf, H.Nguyen, J.Gao, E.T.Powers, M.Gruebele, and J.W.Kelly (2008).
Understanding the mechanism of beta-sheet folding from a chemical and biological perspective.
  Biopolymers, 90, 751-758.  
17905840 T.R.Weikl (2008).
Transition states in protein folding kinetics: modeling phi-values of small beta-sheet proteins.
  Biophys J, 94, 929-937.  
18554060 Z.Luo, J.Ding, and Y.Zhou (2008).
Folding mechanisms of individual beta-hairpins in a Go model of Pin1 WW domain by all-atom molecular dynamics simulations.
  J Chem Phys, 128, 225103.  
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.
  Protein Sci, 16, 2306-2313.  
17174331 R.Day, and V.Daggett (2007).
Direct observation of microscopic reversibility in single-molecule protein folding.
  J Mol Biol, 366, 677-686.  
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.
  Protein Sci, 16, 2233-2239.  
17513360 Z.Luo, J.Ding, and Y.Zhou (2007).
Temperature-dependent folding pathways of Pin1 WW domain: an all-atom molecular dynamics simulation of a Gō model.
  Biophys J, 93, 2152-2161.  
16603501 C.D.Geierhaas, R.B.Best, E.Paci, M.Vendruscolo, and J.Clarke (2006).
Structural comparison of the two alternative transition states for folding of TI I27.
  Biophys J, 91, 263-275.  
16575938 J.Przezdziak, S.Tremmel, I.Kretzschmar, M.Beyermann, M.Bienert, and R.Volkmer-Engert (2006).
Probing the ligand-binding specificity and analyzing the folding state of SPOT-synthesized FBP28 WW domain variants.
  Chembiochem, 7, 780-788.  
16807295 M.Jäger, Y.Zhang, J.Bieschke, H.Nguyen, M.Dendle, M.E.Bowman, J.P.Noel, M.Gruebele, and J.W.Kelly (2006).
Structure-function-folding relationship in a WW domain.
  Proc Natl Acad Sci U S A, 103, 10648-10653.
PDB codes: 1zcn 2f21
17060612 N.Ferguson, J.Becker, H.Tidow, S.Tremmel, T.D.Sharpe, G.Krause, J.Flinders, M.Petrovich, J.Berriman, H.Oschkinat, and A.R.Fersht (2006).
General structural motifs of amyloid protofilaments.
  Proc Natl Acad Sci U S A, 103, 16248-16253.
PDB code: 2nnt
16533840 Y.Mu, L.Nordenskiöld, and J.P.Tam (2006).
Folding, misfolding, and amyloid protofibril formation of WW domain FBP28.
  Biophys J, 90, 3983-3992.  
15383660 A.R.Fersht (2004).
Relationship of Leffler (Bronsted) alpha values and protein folding Phi values to position of transition-state structures on reaction coordinates.
  Proc Natl Acad Sci U S A, 101, 14338-14342.  
15102453 J.Kubelka, J.Hofrichter, and W.A.Eaton (2004).
The protein folding 'speed limit'.
  Curr Opin Struct Biol, 14, 76-88.  
15229605 S.Deechongkit, H.Nguyen, E.T.Powers, P.E.Dawson, M.Gruebele, and J.W.Kelly (2004).
Context-dependent contributions of backbone hydrogen bonding to beta-sheet folding energetics.
  Nature, 430, 101-105.  
14500877 C.M.Kraemer-Pecore, J.T.Lecomte, and J.R.Desjarlais (2003).
A de novo redesign of the WW domain.
  Protein Sci, 12, 2194-2205.  
12651955 H.Nguyen, M.Jager, A.Moretto, M.Gruebele, and J.W.Kelly (2003).
Tuning the free-energy landscape of a WW domain by temperature, mutation, and truncation.
  Proc Natl Acad Sci U S A, 100, 3948-3953.  
12581663 N.Ferguson, and A.R.Fersht (2003).
Early events in protein folding.
  Curr Opin Struct Biol, 13, 75-81.  
12897238 N.Ferguson, J.Berriman, M.Petrovich, T.D.Sharpe, J.T.Finch, and A.R.Fersht (2003).
Rapid amyloid fiber formation from the fast-folding WW domain FBP28.
  Proc Natl Acad Sci U S A, 100, 9814-9819.  
14595026 S.Gianni, N.R.Guydosh, F.Khan, T.D.Caldas, U.Mayor, G.W.White, M.L.DeMarco, V.Daggett, and A.R.Fersht (2003).
Unifying features in protein-folding mechanisms.
  Proc Natl Acad Sci U S A, 100, 13286-13291.  
12471608 T.Wang, and R.C.Wade (2003).
Implicit solvent models for flexible protein-protein docking by molecular dynamics simulation.
  Proteins, 50, 158-169.  
12594518 U.Mayor, N.R.Guydosh, C.M.Johnson, J.G.Grossmann, S.Sato, G.S.Jas, S.M.Freund, D.O.Alonso, V.Daggett, and A.R.Fersht (2003).
The complete folding pathway of a protein from nanoseconds to microseconds.
  Nature, 421, 863-867.  
14671331 Y.Zhu, D.O.Alonso, K.Maki, C.Y.Huang, S.J.Lahr, V.Daggett, H.Roder, W.F.DeGrado, and F.Gai (2003).
Ultrafast folding of alpha3D: a de novo designed three-helix bundle protein.
  Proc Natl Acad Sci U S A, 100, 15486-15491.  
12140363 A.Ghosh, R.Elber, and H.A.Scheraga (2002).
An atomically detailed study of the folding pathways of protein A with the stochastic difference equation.
  Proc Natl Acad Sci U S A, 99, 10394-10398.  
12388785 A.R.Fersht (2002).
On the simulation of protein folding by short time scale molecular dynamics and distributed computing.
  Proc Natl Acad Sci U S A, 99, 14122-14125.  
11909527 A.R.Fersht, and V.Daggett (2002).
Protein folding and unfolding at atomic resolution.
  Cell, 108, 573-582.  
11983864 J.Gsponer, and A.Caflisch (2002).
Molecular dynamics simulations of protein folding from the transition state.
  Proc Natl Acad Sci U S A, 99, 6719-6724.  
11687613 N.Ferguson, C.M.Johnson, M.Macias, H.Oschkinat, and A.Fersht (2001).
Ultrafast folding of WW domains without structured aromatic clusters in the denatured state.
  Proc Natl Acad Sci U S A, 98, 13002-13007.  
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 codes are shown on the right.