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PDBsum entry 2pee

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protein ligands Protein-protein interface(s) links
Hydrolase inhibitor PDB id
2pee
Jmol PyMol
Contents
Protein chains
387 a.a. *
Ligands
SO4
GOL ×2
Waters ×38
* Residue conservation analysis
PDB id:
2pee
Name: Hydrolase inhibitor
Title: Crystal structure of a thermophilic serpin, tengpin, in the state
Structure: Serine protease inhibitor. Chain: a, b. Engineered: yes. Mutation: yes
Source: Thermoanaerobacter tengcongensis. Organism_taxid: 273068. Strain: mb4. Expressed in: escherichia coli. Expression_system_taxid: 562
Resolution:
2.70Å     R-factor:   0.197     R-free:   0.235
Authors: Q.W.Zhang,A.M.Buckle,J.C.Whisstock
Key ref:
Q.Zhang et al. (2007). The N terminus of the serpin, tengpin, functions to trap the metastable native state. EMBO Rep, 8, 658-663. PubMed id: 17557112 DOI: 10.1038/sj.embor.7400986
Date:
02-Apr-07     Release date:   19-Jun-07    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q8R9P5  (Q8R9P5_THETN) -  Serine protease inhibitor
Seq:
Struc:
423 a.a.
387 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular space   1 term 
  Biological process     proteolysis   1 term 
  Biochemical function     peptidase activity     1 term  

 

 
DOI no: 10.1038/sj.embor.7400986 EMBO Rep 8:658-663 (2007)
PubMed id: 17557112  
 
 
The N terminus of the serpin, tengpin, functions to trap the metastable native state.
Q.Zhang, A.M.Buckle, R.H.Law, M.C.Pearce, L.D.Cabrita, G.J.Lloyd, J.A.Irving, A.I.Smith, K.Ruzyla, J.Rossjohn, S.P.Bottomley, J.C.Whisstock.
 
  ABSTRACT  
 
Serpins fold to a metastable native state and are susceptible to undergoing spontaneous conformational change to more stable conformers, such as the latent form. We investigated conformational change in tengpin, an unusual prokaryotic serpin from the extremophile Thermoanaerobacter tengcongensis. In addition to the serpin domain, tengpin contains a functionally uncharacterized 56-amino-acid amino-terminal region. Deletion of this domain creates a variant--tengpinDelta51--which folds past the native state and readily adopts the latent conformation. Analysis of crystal structures together with mutagenesis studies show that the N terminus of tengpin protects a hydrophobic patch in the serpin domain and functions to trap tengpin in its native metastable state. A 13-amino-acid peptide derived from the N terminus is able to mimick the role of the N terminus in stabilizing the native state of tengpinDelta51. Therefore, the function of the N terminus in tengpin resembles protein cofactors that prevent mammalian serpins from spontaneously adopting the latent conformation.
 
  Selected figure(s)  
 
Figure 1.
Figure 1 Crystal structures of tengpin. (A) Structure of native tengpin 31. Elements of secondary structure are labelled. The A -sheet is in shown in red; B -sheet in green; C -sheet in yellow and -helices are in cyan; the reactive centre loop (RCL) is in magenta and the N-terminal region is shown in purple. Tengpin contains 42 of the 51 highly conserved residues present in most serpins; substitutions at these positions are generally conservative. The number of salt bridges of the surface of tengpin (78) is also comparable with other mesophilic and thermophilic counterparts (Fulton et al, 2005). Notably, 21 amino acids of the amino terminus of the serpin domain could be fully resolved in electron density; these residues adopt an extended conformation and form several interactions with the D-helix (supplementary Table 1 online). (B) Structure of latent tengpin 51. Colouring as for (A). A structural comparison of the native and latent conformations of tengpin shows that strands s3A, s2A and s1A, together with the E- and F-helix, shift to accommodate the RCL as a fourth strand in the A -sheet. Conformational changes in strands s3C and s4C are apparent as a result of the transition to the latent state and the repositioning of s1C. The shutter region is indicated. (C) The contacts between the N terminus, helices E, F and A sheet strands 1 and 2 of tengpin 31. Side chains from the A-sheet are in red, from -helices in cyan and from the N terminus in yellow. Dashed lines indicate hydrogen bonds. (D) Comparison of the binding sites of the N terminus (purple) and tengpin (left) with that of the somatomedin B (SMB) domain of vitronectin (purple) and plasminogen activator inhibitor-1 (PAI-1, right; Zhou et al, 2003).
Figure 3.
Figure 3 Cartoon of latent tengpin 51 and tengpin 31. The figure shows how the side chains of residues L41 and M42, in the native state, protect the hydrophobic pocket formed by residues L159, I162 and I170.
 
  The above figures are reprinted from an Open Access publication published by Macmillan Publishers Ltd: EMBO Rep (2007, 8, 658-663) copyright 2007.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21404103 R.E.Fosado-Quiroz, and A.Rojo-Domínguez (2011).
Metastability of papain and the molecular mechanism for its sequential acid-denaturation.
  Protein J, 30, 184-193.  
19953505 D.Belorgey, P.Hägglöf, M.Onda, and D.A.Lomas (2010).
pH-dependent stability of neuroserpin is mediated by histidines 119 and 138; implications for the control of beta-sheet A and polymerization.
  Protein Sci, 19, 220-228.  
20348296 F.Turroni, E.Foroni, M.O'Connell Motherway, F.Bottacini, V.Giubellini, A.Zomer, A.Ferrarini, M.Delledonne, Z.Zhang, D.van Sinderen, and M.Ventura (2010).
Characterization of the serpin-encoding gene of Bifidobacterium breve 210B.
  Appl Environ Microbiol, 76, 3206-3219.  
21081089 S.Ricagno, M.Pezzullo, A.Barbiroli, M.Manno, M.Levantino, M.G.Santangelo, F.Bonomi, and M.Bolognesi (2010).
Two latent and two hyperstable polymeric forms of human neuroserpin.
  Biophys J, 99, 3402-3411.  
19136720 J.H.Baek, W.S.Yang, C.Lee, and M.H.Yu (2009).
Functional unfolding of alpha1-antitrypsin probed by hydrogen-deuterium exchange coupled with mass spectrometry.
  Mol Cell Proteomics, 8, 1072-1081.  
18972012 J.C.Whisstock, and S.P.Bottomley (2008).
Structural biology: Serpins' mystery solved.
  Nature, 455, 1189-1190.  
18063751 R.H.Law, T.Sofian, W.T.Kan, A.J.Horvath, C.R.Hitchen, C.G.Langendorf, A.M.Buckle, J.C.Whisstock, and P.B.Coughlin (2008).
X-ray crystal structure of the fibrinolysis inhibitor alpha2-antiplasmin.
  Blood, 111, 2049-2052.
PDB code: 2r9y
17635906 L.D.Cabrita, J.A.Irving, M.C.Pearce, J.C.Whisstock, and S.P.Bottomley (2007).
Aeropin from the extremophile Pyrobaculum aerophilum bypasses the serpin misfolding trap.
  J Biol Chem, 282, 26802-26809.  
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.

 

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