PDBsum entry 2vh4

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protein Protein-protein interface(s) links
Hydrolase inhibitor PDB id
Protein chains
380 a.a. *
Waters ×240
* Residue conservation analysis
PDB id:
Name: Hydrolase inhibitor
Title: Structure of a loop c-sheet serpin polymer
Structure: Tengpin. Chain: a, b. Fragment: serpin, residues 43-423. Synonym: serine protease inhibitor. Engineered: yes
Source: Thermoanaerobacter tengcongensis. Organism_taxid: 273068. Strain: mb4. Expressed in: escherichia coli. Expression_system_taxid: 562.
2.45Å     R-factor:   0.196     R-free:   0.262
Authors: Q.Zhang,R.H.P.Law,S.P.Bottomley,J.C.Whisstock,A.M.Buckle
Key ref:
Q.Zhang et al. (2008). A structural basis for loop C-sheet polymerization in serpins. J Mol Biol, 376, 1348-1359. PubMed id: 18234218 DOI: 10.1016/j.jmb.2007.12.050
19-Nov-07     Release date:   08-Jan-08    
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Protein chains
Pfam   ArchSchema ?
Q8R9P5  (Q8R9P5_THETN) -  Serine protease inhibitor
423 a.a.
380 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: 10.1016/j.jmb.2007.12.050 J Mol Biol 376:1348-1359 (2008)
PubMed id: 18234218  
A structural basis for loop C-sheet polymerization in serpins.
Q.Zhang, R.H.Law, S.P.Bottomley, J.C.Whisstock, A.M.Buckle.
In this study, we report the X-ray crystal structure of an N-terminally truncated variant of the bacterial serpin, tengpin (tengpinDelta42). Our data reveal that tengpinDelta42 adopts a variation of the latent conformation in which the reactive center loop is hyperinserted into the A beta-sheet and removed from the vicinity of the C-sheet. This conformational change leaves the C beta-sheet completely exposed and permits antiparallel edge-strand interactions between the exposed portion of the reactive center loop of one molecule and strand s2C of the C beta-sheet of the neighboring molecule in the crystal lattice. Our structural data thus reveal that tengpinDelta42 forms a loop C-sheet polymer in the crystal lattice. In vivo serpins have a propensity to misfold and form long-chain polymers, a process that underlies serpinopathies such as emphysema, thrombosis and dementia. Native serpins are thought to polymerize via a loop A-sheet mechanism. However, studies on plasminogen activator inhibitor 1 and the S49P variant of human neuroserpin reveal that the latent form of these molecules can also polymerize. Polymerization of latent neuroserpin may be important for the development of familial encephalopathy with neuroserpin inclusion bodies. Our structural data provide a possible mechanism for polymerization by latent serpins.
  Selected figure(s)  
Figure 1.
Fig. 1. Schematic representation of the conformational states of serpins. The A β-sheet is in red, the C β-sheet is in yellow, the RCL is in magenta and the protease is in cyan.
Figure 6.
Fig. 6. Nondenaturing 12% (wt/vol) PAGE. TP-L: latent tengpinΔ42 polymer (dissolved crystals used for structural analysis); TP-N: native tengpinΔ31 polymer (after prior heating at 80 °C).
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2008, 376, 1348-1359) copyright 2008.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21280127 L.C.Thompson, S.Goswami, D.S.Ginsberg, D.E.Day, I.M.Verhamme, and C.B.Peterson (2011).
Metals affect the structure and activity of human plasminogen activator inhibitor-1. I. Modulation of stability and protease inhibition.
  Protein Sci, 20, 353-365.  
20731544 J.A.Huntington, and J.C.Whisstock (2010).
Molecular contortionism - on the physical limits of serpin 'loop-sheet' polymers.
  Biol Chem, 391, 973-982.  
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.  
19245336 B.Gooptu, and D.A.Lomas (2009).
Conformational pathology of the serpins: themes, variations, and therapeutic strategies.
  Annu Rev Biochem, 78, 147-176.  
18794298 Y.Tsutsui, B.Kuri, T.Sengupta, and P.L.Wintrode (2008).
The structural basis of serpin polymerization studied by hydrogen/deuterium exchange and mass spectrometry.
  J Biol Chem, 283, 30804-30811.  
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.