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PDBsum entry 3t1p
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Hydrolase inhibitor
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PDB id
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3t1p
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PDB id:
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| Name: |
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Hydrolase inhibitor
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Title:
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Crystal structure of an alpha-1-antitrypsin trimer
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Structure:
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Alpha-1-antitrypsin. Chain: a. Fragment: unp residues 48-418. Synonym: alpha-1 protease inhibitor, alpha-1-antiproteinase, serpin a1, short peptide from aat, spaat. Engineered: yes. Mutation: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: serpina1, aat, pi, pro0684, pro2209. Expressed in: escherichia coli. Expression_system_taxid: 562
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Resolution:
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3.90Å
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R-factor:
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0.238
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R-free:
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0.297
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Authors:
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J.A.Huntington,M.Yamasaki
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Key ref:
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M.Yamasaki
et al.
(2011).
Molecular basis of α1-antitrypsin deficiency revealed by the structure of a domain-swapped trimer.
EMBO Rep,
12,
1011-1017.
PubMed id:
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Date:
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22-Jul-11
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Release date:
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17-Aug-11
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PROCHECK
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Headers
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References
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P01009
(A1AT_HUMAN) -
Alpha-1-antitrypsin from Homo sapiens
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Seq:
Struc:
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418 a.a.
371 a.a.*
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Key: |
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PfamA domain |
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Secondary structure |
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CATH domain |
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*
PDB and UniProt seqs differ
at 4 residue positions (black
crosses)
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EMBO Rep
12:1011-1017
(2011)
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PubMed id:
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Molecular basis of α1-antitrypsin deficiency revealed by the structure of a domain-swapped trimer.
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M.Yamasaki,
T.J.Sendall,
M.C.Pearce,
J.C.Whisstock,
J.A.Huntington.
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ABSTRACT
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α(1)-Antitrypsin (α1AT) deficiency is a disease with multiple manifestations,
including cirrhosis and emphysema, caused by the accumulation of stable polymers
of mutant protein in the endoplasmic reticulum of hepatocytes. However, the
molecular basis of misfolding and polymerization remain unknown. We produced and
crystallized a trimeric form of α1AT that is recognized by an antibody specific
for the pathological polymer. Unexpectedly, this structure reveals a polymeric
linkage mediated by domain swapping the carboxy-terminal 34 residues.
Disulphide-trapping and antibody-binding studies further demonstrate that
runaway C-terminal domain swapping, rather than the s4A/s5A domain swap
previously proposed, underlies polymerization of the common Z-mutant of α1AT in
vivo.
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Links
