PDBsum entry 2qug

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protein links
Protease inhibitor PDB id
Protein chain
369 a.a. *
Waters ×46
* Residue conservation analysis
PDB id:
Name: Protease inhibitor
Title: Crystal structure of alpha-1-antitrypsin, crystal form a
Structure: Alpha-1-antitrypsin. Chain: a. Synonym: alpha-1 protease inhibitor, alpha-1-antiproteinase engineered: yes
Source: Homo sapiens. Human. Gene: serpina1, aat, pi. Expressed in: escherichia coli
2.00Å     R-factor:   0.218     R-free:   0.275
Authors: G.Hansen,C.J.Morton,M.C.Pearce,S.C.Feil,J.J.Adams,M.W.Parker S.P.Bottomley
Key ref:
M.C.Pearce et al. (2008). Preventing serpin aggregation: The molecular mechanism of citrate action upon antitrypsin unfolding. Protein Sci, 17, 2127-2133. PubMed id: 18780818 DOI: 10.1110/ps.037234.108
05-Aug-07     Release date:   12-Aug-08    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P01009  (A1AT_HUMAN) -  Alpha-1-antitrypsin
418 a.a.
369 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 region   7 terms 
  Biological process     negative regulation of serine-type endopeptidase activity   19 terms 
  Biochemical function     protein binding     7 terms  


DOI no: 10.1110/ps.037234.108 Protein Sci 17:2127-2133 (2008)
PubMed id: 18780818  
Preventing serpin aggregation: The molecular mechanism of citrate action upon antitrypsin unfolding.
M.C.Pearce, C.J.Morton, S.C.Feil, G.Hansen, J.J.Adams, M.W.Parker, S.P.Bottomley.
The aggregation of antitrypsin into polymers is one of the causes of neonatal hepatitis, cirrhosis, and emphysema. A similar reaction resulting in disease can occur in other human serpins, and collectively they are known as the serpinopathies. One possible therapeutic strategy involves inhibiting the conformational changes involved in antitrypsin aggregation. The citrate ion has previously been shown to prevent antitrypsin aggregation and maintain the protein in an active conformation; its mechanism of action, however, is unknown. Here we demonstrate that the citrate ion prevents the initial misfolding of the native state to a polymerogenic intermediate in a concentration-dependent manner. Furthermore, we have solved the crystal structure of citrate bound to antitrypsin and show that a single citrate molecule binds in a pocket between the A and B beta-sheets, a region known to be important in maintaining antitrypsin stability.
  Selected figure(s)  
Figure 3.
Diagrammatic representation of the three-dimensional structure of the AAT --citrate complex. The protein is shown in ribbon style, with sheet A in blue, sheet B in red, sheet C in yellow, the reactive center loop in green, and the citrate ion is shown as cyan-colored spheres.
Figure 4.
Analysis of the citrate-binding pocket. Stereoscopic figure of residues contributing to the citrate-binding pocket in (A) crystal form A, (B) crystal form B, and (C) the citrate complex. In all three, the protein is shown as sticks colored by atom type (carbon: green, oxygen: red, nitrogen: blue, sulfur: yellow), with water molecules shown as red spheres. In crystal form B, the chloride ion is shown as an orange sphere (B) while in the citrate complex (B) the citrate is shown as sticks colored by atom type, except that the carbon atoms are in cyan. Comparison of the three sites shows that minimal rearrangement of the site has occurred to adapt to citrate binding.
  The above figures are reprinted from an Open Access publication published by the Protein Society: Protein Sci (2008, 17, 2127-2133) copyright 2008.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
19495939 E.Karnaukhova (2010).
Interactions of alpha1-proteinase inhibitor with small ligands of therapeutic potential: binding with retinoic acid.
  Amino Acids, 38, 1011-1020.  
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