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PDBsum entry 1hp7

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protein ligands metals links
Protein binding PDB id
1hp7
Jmol
Contents
Protein chain
376 a.a. *
Ligands
BME
Metals
_ZN ×5
Waters ×95
* Residue conservation analysis
PDB id:
1hp7
Name: Protein binding
Title: A 2.1 angstrom structure of an uncleaved alpha-1-antitrypsin variability of the reactive center and other loops
Structure: Alpha-1-antitrypsin. Chain: a. Engineered: yes. Mutation: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Dimer (from PQS)
Resolution:
2.10Å     R-factor:   0.219     R-free:   0.273
Authors: S.-J.Kim,J.-R.Woo,E.J.Seo,M.-H.Yu,S.-E.Ryu
Key ref:
S.Kim et al. (2001). A 2.1 A resolution structure of an uncleaved alpha(1)-antitrypsin shows variability of the reactive center and other loops. J Mol Biol, 306, 109-119. PubMed id: 11178897 DOI: 10.1006/jmbi.2000.4357
Date:
12-Dec-00     Release date:   14-Mar-01    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P01009  (A1AT_HUMAN) -  Alpha-1-antitrypsin
Seq:
Struc:
418 a.a.
376 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   6 terms 
  Biological process     response to inorganic substance   19 terms 
  Biochemical function     protein binding     6 terms  

 

 
DOI no: 10.1006/jmbi.2000.4357 J Mol Biol 306:109-119 (2001)
PubMed id: 11178897  
 
 
A 2.1 A resolution structure of an uncleaved alpha(1)-antitrypsin shows variability of the reactive center and other loops.
S.Kim, J.Woo, E.J.Seo, M.Yu, S.Ryu.
 
  ABSTRACT  
 
Serpin (serine protease inhibitor) proteins are involved in diverse physiological processes including inflammation, coagulation, matrix remodeling, and cell differentiation. Deficiency of normal serpin functions leads to various hereditary diseases. Besides their clinical importance, serpin proteins draw much attention due to the large conformational changes that occur upon interaction with proteases. We present here the crystal structure of an uncleaved alpha(1)-antitrypsin determined by the multiple isomorphous replacement method and refined to 2.1 A resolution. The structure, which is the first active serpin structure based on experimental phases, reveals novel conformations in the flexible loops, including the proximal hinge region of the reactive center loop and the surface cavity region in the central beta-sheet, sheet A. The determined loop conformation explains the results of recent mutagenesis studies and provides detailed insights into the protease inhibition mechanism. The high-resolution structure of active alpha(1)-antitrypsin also provides evidence for the existence of localized van-der-Waals strain in the central hydrophobic core.
 
  Selected figure(s)  
 
Figure 5.
Figure 5. Interactions of the distal hinge region. The side-chains of residues important for the maintenance of the canonical loop structure and the b-strand confor- mation of the RCL are shown as ball-and-stick represen- tations on a C a warm diagram trace in stereo. For the Arg223 to Gly225 region, all atoms were drawn as a ball-and-stick representation to indicate the main chain hydrogen bond with Wat86. The representative hydro- gen bonds are depicted as broken lines.
Figure 7.
Figure 7. Location of surface cavities and the surrounding side-chains. The surface cavities of the A70G structure were investigated by using the program VOIDOO (Kleywegt & Jones, 1994). The two prominent cavities, which were found in the right side of the molecule, are drawn as a basket-weave model (brown) on a ribbon diagram. (a) The cavities (cav. 1 and cav. 2) are drawn on a ribbon diagram to show the location of the cavities in the context of the whole molecule. The N and C termini are also labeled. (b) Close-up view of the cavity region. The residues surround- ing the first cavity (cav. 1) are shown as a ball-and-stick representation. The side-chain of the glycosylation site (Asn247) is also drawn as a ball-and-stick diagram.
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2001, 306, 109-119) copyright 2001.  
  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.  
19435496 A.Mulenga, R.Khumthong, and K.C.Chalaire (2009).
Ixodes scapularis tick serine proteinase inhibitor (serpin) gene family; annotation and transcriptional analyses.
  BMC Genomics, 10, 217.  
19492109 C.Boudier, A.S.Klymchenko, Y.Mely, and A.Follenius-Wund (2009).
Local environment perturbations in alpha(1)-antitrypsin monitored by a ratiometric fluorescent label.
  Photochem Photobiol Sci, 8, 814-821.  
19426146 U.I.Ekeowa, B.Gooptu, D.Belorgey, P.Hägglöf, S.Karlsson-Li, E.Miranda, J.Pérez, I.MacLeod, H.Kroger, S.J.Marciniak, D.C.Crowther, and D.A.Lomas (2009).
alpha1-Antitrypsin deficiency, chronic obstructive pulmonary disease and the serpinopathies.
  Clin Sci (Lond), 116, 837-850.  
18453687 T.C.Terwilliger, R.W.Grosse-Kunstleve, P.V.Afonine, N.W.Moriarty, P.D.Adams, R.J.Read, P.H.Zwart, and L.W.Hung (2008).
Iterative-build OMIT maps: map improvement by iterative model building and refinement without model bias.
  Acta Crystallogr D Biol Crystallogr, 64, 515-524.  
  19164889 D.Belorgey, P.Hägglöf, S.Karlsson-Li, and D.A.Lomas (2007).
Protein misfolding and the serpinopathies.
  Prion, 1, 15-20.  
17644521 M.A.Klieber, C.Underhill, G.L.Hammond, and Y.A.Muller (2007).
Corticosteroid-binding globulin, a structural basis for steroid transport and proteinase-triggered release.
  J Biol Chem, 282, 29594-29603.
PDB codes: 2v6d 2v95
15170041 D.A.Lomas, and H.Parfrey (2004).
Alpha1-antitrypsin deficiency. 4: Molecular pathophysiology.
  Thorax, 59, 529-535.  
12807889 H.Parfrey, R.Mahadeva, N.A.Ravenhill, A.Zhou, T.R.Dafforn, R.C.Foreman, and D.A.Lomas (2003).
Targeting a surface cavity of alpha 1-antitrypsin to prevent conformational disease.
  J Biol Chem, 278, 33060-33066.  
11834734 E.J.Seo, C.Lee, and M.H.Yu (2002).
Concerted regulation of inhibitory activity of alpha 1-antitrypsin by the native strain distributed throughout the molecule.
  J Biol Chem, 277, 14216-14220.  
12244055 H.Im, M.S.Woo, K.Y.Hwang, and M.H.Yu (2002).
Interactions causing the kinetic trap in serpin protein folding.
  J Biol Chem, 277, 46347-46354.
PDB code: 1iz2
12009885 S.W.Griffiths, and C.L.Cooney (2002).
Relationship between protein structure and methionine oxidation in recombinant human alpha 1-antitrypsin.
  Biochemistry, 41, 6245-6252.  
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.