PDBsum entry 1tud

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protein links
Cytoskeleton PDB id
Protein chain
60 a.a. *
Waters ×57
* Residue conservation analysis
PDB id:
Name: Cytoskeleton
Title: Alpha-spectrin src homology 3 domain, circular permutant, cut at n47-d48
Structure: Alpha-spectrin. Chain: a. Fragment: src homology 3 domain. Engineered: yes. Mutation: yes. Other_details: this is a circular permutant of the wt alpha-spectrin sh3 sequence (PDB code wt-3d structure: 1sgb). The residue numbers are as in the wt spectrin-sh3 domain (1sgb). Thr 4 (n-terminus) and asp 62 (c-terminus)
Source: Gallus gallus. Chicken. Organism_taxid: 9031. Organ: brain. Expressed in: escherichia coli. Expression_system_taxid: 562.
1.77Å     R-factor:   0.184     R-free:   0.248
Authors: A.R.Viguera,L.Serrano,M.Wilmanns
Key ref: A.R.Viguera et al. (1995). The order of secondary structure elements does not determine the structure of a protein but does affect its folding kinetics. J Mol Biol, 247, 670-681. PubMed id: 7723022 DOI: 10.1006/jmbi.1994.0171
29-Feb-96     Release date:   01-Aug-96    
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Protein chain
Pfam   ArchSchema ?
P07751  (SPTA2_CHICK) -  Spectrin alpha chain, non-erythrocytic 1
2477 a.a.
60 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 13 residue positions (black crosses)


DOI no: 10.1006/jmbi.1994.0171 J Mol Biol 247:670-681 (1995)
PubMed id: 7723022  
The order of secondary structure elements does not determine the structure of a protein but does affect its folding kinetics.
A.R.Viguera, F.J.Blanco, L.Serrano.
We have analyzed the structure, stability and folding kinetics of circularly permuted forms of alpha-spectrin SH3 domain. All the possible permutations involving the disruption of the covalent linkage between two beta-strands forming a beta-hairpin have been done. The different proteins constructed here fold to a native conformation similar to that of wild-type protein, as demonstrated by nuclear magnetic resonance and circular dichroism. Although all the mutants have similar stabilities (they are 1 to 2 kcal mol-1 less stable than the wild-type) their rate constants for folding and unfolding are quite different. Protein engineering, in combination with kinetics indicates that the folding pathway has been changed in the circularly permuted proteins. We conclude that neither the order of secondary structure elements, nor the preservation of any of the beta-hairpins present in this domain, is crucial for the ability of the polypeptide to fold, but they influence the folding and unfolding kinetics and could determine its folding pathway.

Literature references that cite this PDB file's key reference

  PubMed id Reference
21087800 Y.Yu, and S.Lutz (2011).
Circular permutation: a different way to engineer enzyme structure and function.
  Trends Biotechnol, 29, 18-25.  
19966410 A.Cámara-Artigas, M.Andújar-Sánchez, E.Ortiz-Salmerón, C.Cuadri, and S.Casares (2009).
The effect of a proline residue on the rate of growth and the space group of alpha-spectrin SH3-domain crystals.
  Acta Crystallogr D Biol Crystallogr, 65, 1247-1252.
PDB code: 3i9q
19617233 A.M.Candel, E.S.Cobos, F.Conejero-Lara, and J.C.Martinez (2009).
Evaluation of folding co-operativity of a chimeric protein based on the molecular recognition between polyproline ligands and SH3 domains.
  Protein Eng Des Sel, 22, 597-606.  
19683009 Z.Qian, J.R.Horton, X.Cheng, and S.Lutz (2009).
Structural redesign of lipase B from Candida antarctica by circular permutation and incremental truncation.
  J Mol Biol, 393, 191-201.
PDB codes: 3icv 3icw
18005453 A.Abyzov, and V.A.Ilyin (2007).
A comprehensive analysis of non-sequential alignments between all protein structures.
  BMC Struct Biol, 7, 78.  
17962398 J.Carey, S.Lindman, M.Bauer, and S.Linse (2007).
Protein reconstitution and three-dimensional domain swapping: benefits and constraints of covalency.
  Protein Sci, 16, 2317-2333.  
16891373 H.X.Zhou (2006).
Quantitative relation between intermolecular and intramolecular binding of pro-rich peptides to SH3 domains.
  Biophys J, 91, 3170-3181.  
16266719 D.L.Theobald, and D.S.Wuttke (2005).
Divergent evolution within protein superfolds inferred from profile-based phylogenetics.
  J Mol Biol, 354, 722-737.  
16198264 M.Kojima, K.Ayabe, and H.Ueda (2005).
Importance of terminal residues on circularly permutated Escherichia coli alkaline phosphatase with high specific activity.
  J Biosci Bioeng, 100, 197-202.  
15531601 X.Yuan, and C.Bystroff (2005).
Non-sequential structure-based alignments reveal topology-independent core packing arrangements in proteins.
  Bioinformatics, 21, 1010-1019.  
14691236 H.Fan, and A.E.Mark (2004).
Refinement of homology-based protein structures by molecular dynamics simulation techniques.
  Protein Sci, 13, 211-220.  
15136744 L.Hedberg, and M.Oliveberg (2004).
Scattered Hammond plots reveal second level of site-specific information in protein folding: phi' (beta++).
  Proc Natl Acad Sci U S A, 101, 7606-7611.  
12736261 A.V.Cheltsov, W.C.Guida, and G.C.Ferreira (2003).
Circular permutation of 5-aminolevulinate synthase: effect on folding, conformational stability, and structure.
  J Biol Chem, 278, 27945-27955.  
12945054 H.Fan, and A.E.Mark (2003).
Relative stability of protein structures determined by X-ray crystallography or NMR spectroscopy: a molecular dynamics simulation study.
  Proteins, 53, 111-120.  
12149462 E.J.Miller, K.F.Fischer, and S.Marqusee (2002).
Experimental evaluation of topological parameters determining protein-folding rates.
  Proc Natl Acad Sci U S A, 99, 10359-10363.  
12461186 J.W.Schymkowitz, F.Rousseau, and L.Serrano (2002).
Surfing on protein folding energy landscapes.
  Proc Natl Acad Sci U S A, 99, 15846-15848.  
11344321 P.T.Beernink, Y.R.Yang, R.Graf, D.S.King, S.S.Shah, and H.K.Schachman (2001).
Random circular permutation leading to chain disruption within and near alpha helices in the catalytic chains of aspartate transcarbamoylase: effects on assembly, stability, and function.
  Protein Sci, 10, 528-537.  
11173498 R.Berisio, A.Viguera, L.Serrano, and M.Wilmanns (2001).
Atomic resolution structure of a mutant of the spectrin SH3 domain.
  Acta Crystallogr D Biol Crystallogr, 57, 337-340.
PDB code: 1g2b
11344320 X.Ni, and H.K.Schachman (2001).
In vivo assembly of aspartate transcarbamoylase from fragmented and circularly permuted catalytic polypeptide chains.
  Protein Sci, 10, 519-527.  
11150614 A.Planas (2000).
Bacterial 1,3-1,4-beta-glucanases: structure, function and protein engineering.
  Biochim Biophys Acta, 1543, 361-382.  
  11206053 M.C.Vega, J.C.Martínez, and L.Serrano (2000).
Thermodynamic and structural characterization of Asn and Ala residues in the disallowed II' region of the Ramachandran plot.
  Protein Sci, 9, 2322-2328.
PDB codes: 1qkw 1qkx
  10452603 C.J.Tsai, J.V.Maizel, and R.Nussinov (1999).
Distinguishing between sequential and nonsequentially folded proteins: implications for folding and misfolding.
  Protein Sci, 8, 1591-1604.  
9888794 J.C.Martínez, A.R.Viguera, R.Berisio, M.Wilmanns, P.L.Mateo, V.V.Filimonov, and L.Serrano (1999).
Thermodynamic analysis of alpha-spectrin SH3 and two of its circular permutants with different loop lengths: discerning the reasons for rapid folding in proteins.
  Biochemistry, 38, 549-559.
PDB code: 1pwt
10425681 M.J.Scanlon, M.C.Lee, M.A.Anderson, and D.J.Craik (1999).
Structure of a putative ancestral protein encoded by a single sequence repeat from a multidomain proteinase inhibitor gene from Nicotiana alata.
  Structure, 7, 793-802.
PDB code: 1ce3
10383405 T.Nakamura, and M.Iwakura (1999).
Circular permutation analysis as a method for distinction of functional elements in the M20 loop of Escherichia coli dihydrofolate reductase.
  J Biol Chem, 274, 19041-19047.  
10872466 W.F.DeGrado, C.M.Summa, V.Pavone, F.Nastri, and A.Lombardi (1999).
De novo design and structural characterization of proteins and metalloproteins.
  Annu Rev Biochem, 68, 779-819.  
9519300 A.P.Capaldi, and S.E.Radford (1998).
Kinetic studies of beta-sheet protein folding.
  Curr Opin Struct Biol, 8, 86-92.  
9609709 D.E.Otzen, and A.R.Fersht (1998).
Folding of circular and permuted chymotrypsin inhibitor 2: retention of the folding nucleus.
  Biochemistry, 37, 8139-8146.  
9699637 J.C.Martinez, M.T.Pisabarro, and L.Serrano (1998).
Obligatory steps in protein folding and the conformational diversity of the transition state.
  Nat Struct Biol, 5, 721-729.
PDB code: 1bk2
9461080 J.Lubkowski, F.Hennecke, A.Plückthun, and A.Wlodawer (1998).
The structural basis of phage display elucidated by the crystal structure of the N-terminal domains of g3p.
  Nat Struct Biol, 5, 140-147.
PDB code: 1g3p
  9521124 K.L.Reid, H.M.Rodriguez, B.J.Hillier, and L.M.Gregoret (1998).
Stability and folding properties of a model beta-sheet protein, Escherichia coli CspA.
  Protein Sci, 7, 470-479.  
9485402 K.W.Plaxco, J.I.Guijarro, C.J.Morton, M.Pitkeathly, I.D.Campbell, and C.M.Dobson (1998).
The folding kinetics and thermodynamics of the Fyn-SH3 domain.
  Biochemistry, 37, 2529-2537.  
9614709 M.Iwakura (1998).
In search of circular permuted variants of Escherichia coli dihydrofolate reductase.
  Biosci Biotechnol Biochem, 62, 778-781.  
9593194 S.García-Vallvé, A.Rojas, J.Palau, and A.Romeu (1998).
Circular permutants in beta-glucosidases (family 3) within a predicted double-domain topology that includes a (beta/alpha)8-barrel.
  Proteins, 31, 214-223.  
9407040 A.N.Fedorov, and T.O.Baldwin (1997).
Cotranslational protein folding.
  J Biol Chem, 272, 32715-32718.  
9360611 A.R.Viguera, and L.Serrano (1997).
Loop length, intramolecular diffusion and protein folding.
  Nat Struct Biol, 4, 939-946.  
9188741 A.V.Efimov (1997).
Structural trees for protein superfamilies.
  Proteins, 28, 241-260.  
  9232644 C.J.Tsai, and R.Nussinov (1997).
Hydrophobic folding units at protein-protein interfaces: implications to protein folding and to protein-protein association.
  Protein Sci, 6, 1426-1437.  
9032061 E.I.Shakhnovich (1997).
Theoretical studies of protein-folding thermodynamics and kinetics.
  Curr Opin Struct Biol, 7, 29-40.  
9171332 M.Boissinot, S.Karnas, J.R.Lepock, D.E.Cabelli, J.A.Tainer, E.D.Getzoff, and R.A.Hallewell (1997).
Function of the Greek key connection analysed using circular permutants of superoxide dismutase.
  EMBO J, 16, 2171-2178.  
9220963 U.Pieper, K.Hayakawa, Z.Li, and O.Herzberg (1997).
Circularly permuted beta-lactamase from Staphylococcus aureus PC1.
  Biochemistry, 36, 8767-8774.
PDB code: 1alq
8836105 A.R.Viguera, L.Serrano, and M.Wilmanns (1996).
Different folding transition states may result in the same native structure.
  Nat Struct Biol, 3, 874-880.  
8612075 H.X.Zhou, R.H.Hoess, and W.F.DeGrado (1996).
In vitro evolution of thermodynamically stable turns.
  Nat Struct Biol, 3, 446-451.  
  8745397 J.B.Garrett, L.S.Mullins, and F.M.Raushel (1996).
Are turns required for the folding of ribonuclease T1?
  Protein Sci, 5, 204-211.  
8756488 J.L.Johnson, and F.M.Raushel (1996).
Influence of primary sequence transpositions on the folding pathways of ribonuclease T1.
  Biochemistry, 35, 10223-10233.  
  8819162 P.Zhang, and H.K.Schachman (1996).
In vivo formation of allosteric aspartate transcarbamoylase containing circularly permuted catalytic polypeptide chains: implications for protein folding and assembly.
  Protein Sci, 5, 1290-1300.  
8876180 R.Graf, and H.K.Schachman (1996).
Random circular permutation of genes and expressed polypeptide chains: application of the method to the catalytic chains of aspartate transcarbamoylase.
  Proc Natl Acad Sci U S A, 93, 11591-11596.  
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.