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PDBsum entry 1d5s

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protein Protein-protein interface(s) links
Hydrolase inhibitor PDB id
1d5s
Jmol
Contents
Protein chains
334 a.a. *
41 a.a. *
* Residue conservation analysis
PDB id:
1d5s
Name: Hydrolase inhibitor
Title: Crystal structure of cleaved antitrypsin polymer
Structure: P1-arg antitrypsin. Chain: a. Fragment: n-terminal fragment. Engineered: yes. P1-arg antitrypsin. Chain: b. Fragment: c-terminal fragment. Engineered: yes. Mutation: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Organ: liver. Expressed in: escherichia coli. Expression_system_taxid: 562. Expression_system_taxid: 562
Biol. unit: Dimer (from PQS)
Resolution:
3.00Å     R-factor:   0.208     R-free:   0.262
Authors: M.A.Dunstone,W.Dai,J.C.Whisstock,J.Rossjohn,R.N.Pike, S.C.Feil,B.F.Le Bonneic,M.W.Parker,S.P.Bottomley
Key ref: M.A.Dunstone et al. (2000). Cleaved antitrypsin polymers at atomic resolution. Protein Sci, 9, 417-420. PubMed id: 10716194 DOI: 10.1110/ps.9.2.417
Date:
11-Oct-99     Release date:   02-Apr-00    
PROCHECK
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 Headers
 References

Protein chain
Pfam   ArchSchema ?
P01009  (A1AT_HUMAN) -  Alpha-1-antitrypsin
Seq:
Struc:
418 a.a.
334 a.a.
Protein chain
Pfam   ArchSchema ?
P01009  (A1AT_HUMAN) -  Alpha-1-antitrypsin
Seq:
Struc:
418 a.a.
41 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 

 

 
DOI no: 10.1110/ps.9.2.417 Protein Sci 9:417-420 (2000)
PubMed id: 10716194  
 
 
Cleaved antitrypsin polymers at atomic resolution.
M.A.Dunstone, W.Dai, J.C.Whisstock, J.Rossjohn, R.N.Pike, S.C.Feil, B.F.Le Bonniec, M.W.Parker, S.P.Bottomley.
 
  ABSTRACT  
 
Alpha1-antitrypsin deficiency, which can lead to both emphysema and liver disease, is a result of the accumulation of alpha1-antitrypsin polymers within the hepatocyte. A wealth of biochemical and biophysical data suggests that alpha1-antitrypsin polymers form via insertion of residues from the reactive center loop of one molecule into the beta-sheet of another. However, this long-standing hypothesis has not been confirmed by direct structural evidence. Here, we describe the first crystallographic evidence of a beta-strand linked polymer form of alpha1-antitrypsin: the crystal structure of a cleaved alpha1-antitrypsin polymer.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
  21383917 P.Singh, and M.A.Jairajpuri (2011).
Strand 6B deformation and residues exposure towards N-terminal end of helix B during proteinase inhibition by Serpins.
  Bioinformation, 5, 315-319.  
20855577 U.I.Ekeowa, J.Freeke, E.Miranda, B.Gooptu, M.F.Bush, J.Pérez, J.Teckman, C.V.Robinson, and D.A.Lomas (2010).
Defining the mechanism of polymerization in the serpinopathies.
  Proc Natl Acad Sci U S A, 107, 17146-17151.  
18785256 A.S.Knaupp, and S.P.Bottomley (2009).
Serpin polymerization and its role in disease--the molecular basis of alpha1-antitrypsin deficiency.
  IUBMB Life, 61, 1-5.  
19232354 B.Gooptu, E.Miranda, I.Nobeli, M.Mallya, A.Purkiss, S.C.Brown, C.Summers, R.L.Phillips, D.A.Lomas, and T.E.Barrett (2009).
Crystallographic and cellular characterisation of two mechanisms stabilising the native fold of alpha1-antitrypsin: implications for disease and drug design.
  J Mol Biol, 387, 857-868.
PDB codes: 3drm 3dru
18267959 E.Miranda, I.MacLeod, M.J.Davies, J.Pérez, K.Römisch, D.C.Crowther, and D.A.Lomas (2008).
The intracellular accumulation of polymeric neuroserpin explains the severity of the dementia FENIB.
  Hum Mol Genet, 17, 1527-1539.  
18573252 R.W.Carrell, A.Mushunje, and A.Zhou (2008).
Serpins show structural basis for oligomer toxicity and amyloid ubiquity.
  FEBS Lett, 582, 2537-2541.  
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.  
17608807 M.C.Pearce, L.D.Cabrita, A.M.Ellisdon, and S.P.Bottomley (2007).
The loss of tryptophan 194 in antichymotrypsin lowers the kinetic barrier to misfolding.
  FEBS J, 274, 3622-3632.  
17442346 P.Chowdhury, W.Wang, S.Lavender, M.R.Bunagan, J.W.Klemke, J.Tang, J.G.Saven, B.S.Cooperman, and F.Gai (2007).
Fluorescence correlation spectroscopic study of serpin depolymerization by computationally designed peptides.
  J Mol Biol, 369, 462-473.  
16737556 R.H.Law, Q.Zhang, S.McGowan, A.M.Buckle, G.A.Silverman, W.Wong, C.J.Rosado, C.G.Langendorf, R.N.Pike, P.I.Bird, and J.C.Whisstock (2006).
An overview of the serpin superfamily.
  Genome Biol, 7, 216.  
16176261 J.C.Whisstock, S.P.Bottomley, P.I.Bird, R.N.Pike, and P.Coughlin (2005).
Serpins 2005 - fun between the beta-sheets. Meeting report based upon presentations made at the 4th International Symposium on Serpin Structure, Function and Biology (Cairns, Australia).
  FEBS J, 272, 4868-4873.  
15170041 D.A.Lomas, and H.Parfrey (2004).
Alpha1-antitrypsin deficiency. 4: Molecular pathophysiology.
  Thorax, 59, 529-535.  
15215529 L.N.Benning, J.C.Whisstock, J.Sun, P.I.Bird, and S.P.Bottomley (2004).
The human serpin proteinase inhibitor-9 self-associates at physiological temperatures.
  Protein Sci, 13, 1859-1864.  
15486938 S.Janciauskiene, S.Eriksson, F.Callea, M.Mallya, A.Zhou, K.Seyama, S.Hata, and D.A.Lomas (2004).
Differential detection of PAS-positive inclusions formed by the Z, Siiyama, and Mmalton variants of alpha1-antitrypsin.
  Hepatology, 40, 1203-1210.  
12360234 D.A.Lomas, and R.W.Carrell (2002).
Serpinopathies and the conformational dementias.
  Nat Rev Genet, 3, 759-768.  
11714919 S.P.Bottomley, I.D.Lawrenson, D.Tew, W.Dai, J.C.Whisstock, and R.N.Pike (2001).
The role of strand 1 of the C beta-sheet in the structure and function of alpha(1)-antitrypsin.
  Protein Sci, 10, 2518-2524.  
11123897 S.Yakovlev, S.Litvinovich, D.Loukinov, and L.Medved (2000).
Role of the beta-strand insert in the central domain of the fibrinogen gamma-module.
  Biochemistry, 39, 15721-15729.  
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.