PDBsum entry 1kct

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Serine protease inhibitor PDB id
Protein chain
375 a.a. *
* Residue conservation analysis
PDB id:
Name: Serine protease inhibitor
Title: Alpha1-antitrypsin
Structure: Alpha1-antitrypsin. Chain: a. Synonym: alpha1-proteinase inhibitor. Engineered: yes. Mutation: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: a1at. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
3.46Å     R-factor:   0.184    
Authors: H.K.Song,S.W.Suh
Key ref:
H.K.Song et al. (1995). Crystal structure of an uncleaved alpha 1-antitrypsin reveals the conformation of its inhibitory reactive loop. FEBS Lett, 377, 150-154. PubMed id: 8543039 DOI: 10.1016/0014-5793(95)01331-8
06-Aug-96     Release date:   11-Jan-97    
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Protein chain
Pfam   ArchSchema ?
P01009  (A1AT_HUMAN) -  Alpha-1-antitrypsin
418 a.a.
375 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 3 residue positions (black crosses)

 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: 10.1016/0014-5793(95)01331-8 FEBS Lett 377:150-154 (1995)
PubMed id: 8543039  
Crystal structure of an uncleaved alpha 1-antitrypsin reveals the conformation of its inhibitory reactive loop.
H.K.Song, K.N.Lee, K.S.Kwon, M.H.Yu, S.W.Suh.
The crystal structure of a recombinant human alpha 1-antitrypsin, in the uncleaved and uncomplexed state, has been determined by X-ray crystallographic methods and refined to an R-factor of 18.4% for 8.0-3.46 A data with good stereochemistry. This structure provides the first view at the inhibitory loop and the central beta-sheet A of the uncleaved alpha 1-antitrypsin. The reactive loop takes a distorted helical conformation and no pre-insertion of two residues in the reactive loop into the beta-sheet A is observed. The present structure is largely in agreement with the model predicted by Engh, Wright, and Huber [Prot. Eng. 3 (1990) 469-477].
  Selected figure(s)  
Figure 1.
Fig. 1. Stereo ribbon diagram of uncleaved a~AT drawn with the progam MOLSCRIPT [22]. The a-helices are represented by helical ibbons and fl-sheets by arrows. The reactive loop residues P15-P5' (Gly344-Glu363) are at the top.
Figure 3.
Fi~. 3. A stereo view of the final (2Fo-Fc) electron density map and the central fl-sheet A of uncleaved ~IAT (in thick lines). The reactive loop of un,.:leaved c~]AT is also shown at the top of the figure. Thin lines in (a) and represent the superposed models of cleaved ~zAT and ovalbumin, respectively. Th strands of the ental fl-sheet A are labelled as s2A, s3A, s4A, s5A, and s6A, respectively. The P15, P1, and P5' of the reactive are also indicated.
  The above figures are reprinted by permission from the Federation of European Biochemical Societies: FEBS Lett (1995, 377, 150-154) copyright 1995.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21498872 T.R.Flotte, and C.Mueller (2011).
Gene therapy for alpha-1 antitrypsin deficiency.
  Hum Mol Genet, 20, R87-R92.  
18380904 G.Schenk, T.Margraf, and A.E.Torda (2008).
Protein sequence and structure alignments within one framework.
  Algorithms Mol Biol, 3, 4.  
16773239 E.Karnaukhova, Y.Ophir, and B.Golding (2006).
Recombinant human alpha-1 proteinase inhibitor: towards therapeutic use.
  Amino Acids, 30, 317-332.  
9988693 V.Picard, P.E.Marque, F.Paolucci, M.Aiach, and B.F.Le Bonniec (1999).
Topology of the stable serpin-protease complexes revealed by an autoantibody that fails to react with the monomeric conformers of antithrombin.
  J Biol Chem, 274, 4586-4593.  
9468513 C.E.Chaillan-Huntington, and P.A.Patston (1998).
Influence of the P5 residue on alpha1-proteinase inhibitor mechanism.
  J Biol Chem, 273, 4569-4573.  
9521649 C.M.Lukacs, H.Rubin, and D.W.Christianson (1998).
Engineering an anion-binding cavity in antichymotrypsin modulates the "spring-loaded" serpin-protease interaction.
  Biochemistry, 37, 3297-3304.
PDB codes: 1as4 3caa 4caa
9521646 J.A.Huntington, and P.G.Gettins (1998).
Conformational conversion of antithrombin to a fully activated substrate of factor Xa without need for heparin.
  Biochemistry, 37, 3272-3277.  
9535901 P.Mellet, C.Boudier, Y.Mely, and J.G.Bieth (1998).
Stopped flow fluorescence energy transfer measurement of the rate constants describing the reversible formation and the irreversible rearrangement of the elastase-alpha1-proteinase inhibitor complex.
  J Biol Chem, 273, 9119-9123.  
9154928 G.Kaslik, J.Kardos, E.Szabó, L.Szilágyi, P.Závodszky, W.M.Westler, J.L.Markley, and L.Gráf (1997).
Effects of serpin binding on the target proteinase: global stabilization, localized increased structural flexibility, and conserved hydrogen bonding at the active site.
  Biochemistry, 36, 5455-5464.  
9342229 R.Egelund, S.L.Schousboe, L.Sottrup-Jensen, K.W.Rodenburg, and P.A.Andreasen (1997).
Type-1 plasminogen-activator inhibitor -- conformational differences between latent, active, reactive-centre-cleaved and plasminogen-activator-complexed forms, as probed by proteolytic susceptibility.
  Eur J Biochem, 248, 775-785.  
8836107 C.M.Lukacs, J.Q.Zhong, M.I.Plotnick, H.Rubin, B.S.Cooperman, and D.W.Christianson (1996).
Arginine substitutions in the hinge region of antichymotrypsin affect serpin beta-sheet rearrangement.
  Nat Struct Biol, 3, 888-893.
PDB codes: 1ct3 2caa
  8931142 D.H.Shin, H.K.Song, I.S.Seong, C.S.Lee, C.H.Chung, and S.W.Suh (1996).
Crystal structure analyses of uncomplexed ecotin in two crystal forms: implications for its function and stability.
  Protein Sci, 5, 2236-2247.
PDB codes: 1ecy 1ecz
  8976566 E.Stratikos, E.Alberdi, P.G.Gettins, and S.P.Becerra (1996).
Recombinant human pigment epithelium-derived factor (PEDF): characterization of PEDF overexpressed and secreted by eukaryotic cells.
  Protein Sci, 5, 2575-2582.  
  8931141 H.Koloczek, A.Banbula, G.S.Salvesen, and J.Potempa (1996).
Serpin alpha 1proteinase inhibitor probed by intrinsic tryptophan fluorescence spectroscopy.
  Protein Sci, 5, 2226-2235.  
8679610 J.A.Huntington, S.T.Olson, B.Fan, and P.G.Gettins (1996).
Mechanism of heparin activation of antithrombin. Evidence for reactive center loop preinsertion with expulsion upon heparin binding.
  Biochemistry, 35, 8495-8503.  
8756699 K.Nordling, and I.Björk (1996).
Identification of an epitope in antithrombin appearing on insertion of the reactive-bond loop into the A beta-sheet.
  Biochemistry, 35, 10436-10440.  
8652540 M.I.Plotnick, L.Mayne, N.M.Schechter, and H.Rubin (1996).
Distortion of the active site of chymotrypsin complexed with a serpin.
  Biochemistry, 35, 7586-7590.  
8756325 P.R.Elliott, D.A.Lomas, R.W.Carrell, and J.P.Abrahams (1996).
Inhibitory conformation of the reactive loop of alpha 1-antitrypsin.
  Nat Struct Biol, 3, 676-681.
PDB code: 1psi
8939743 S.E.Ryu, H.J.Choi, K.S.Kwon, K.N.Lee, and M.H.Yu (1996).
The native strains in the hydrophobic core and flexible reactive loop of a serine protease inhibitor: crystal structure of an uncleaved alpha1-antitrypsin at 2.7 A.
  Structure, 4, 1181-1192.
PDB code: 1atu
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