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PDBsum entry 1tie
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Proteinase inhibitor (trypsin)
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PDB id
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1tie
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References listed in PDB file
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Key reference
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Title
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Crystal structure of a kunitz-Type trypsin inhibitor from erythrina caffra seeds.
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Authors
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S.Onesti,
P.Brick,
D.M.Blow.
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Ref.
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J Mol Biol, 1991,
217,
153-176.
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PubMed id
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Abstract
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The trypsin inhibitor DE-3 from Erythrina caffra (ETI) belongs to the
Kunitz-type soybean trypsin inhibitor (STI) family and consists of 172 amino
acid residues with two disulphide bridges. The amino acid sequence of ETI shows
high homology to other trypsin inhibitors from the same family but ETI has the
unique ability to bind and inhibit tissue plasminogen activator. The crystal
structure of ETI has been determined using the method of isomorphous replacement
and refined using a combination of simulated annealing and conventional
restrained least-squares crystallographic refinement. The refined model includes
60 water molecules and 166 amino acid residues, with a root-mean-square
deviation in bond lengths from ideal values of 0.016 A. The crystallographic
R-factor is 20.8% for 7770 independent reflections between 10.0 and 2.5 A. The
three-dimensional structure of ETI consists of 12 antiparallel beta-strands
joined by long loops. Six of the strands form a short antiparallel beta-barrel
that is closed at one end by a "lid" consisting of the other six strands coupled
in pairs. The molecule shows approximate 3-fold symmetry about the axis of the
barrel, with the repeating unit consisting of four sequential beta-strands and
the connecting loops. Although there is no sequence homology, this same fold is
present in the structure of interleukin-1 alpha and interleukin-1 beta. When the
structure of ETI and interleukin-1 beta are superposed, the close agreement
between the alpha-carbon positions for the beta-strands is striking. The
scissile bond (Arg63-Ser64) is located on an external loop that protrudes from
the surface of the molecule and whose architecture is not constrained by
secondary structure elements, disulphide bridges or strong electrostatic
interactions. The hydrogen bonds made by the side-chain amide group of Asn12
play a key role in maintaining the three-dimensional structure of the loop. This
residue is in a position corresponding to that of a conserved asparagine in the
Kazal inhibitor family. Although the overall structure of ETI is similar to the
partial structure of STI, the scissile bond loop is displaced by about 4 A. This
displacement probably arises from the fact that the structure of STI has been
determined in a complex with trypsin but could possibly be a consequence of the
close molecular contact between Arg63 and an adjacent molecule in the crystal
lattice.
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Secondary reference #1
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Title
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Crystallization and preliminary diffraction studies of erythrina trypsin inhibitor.
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Authors
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S.Onesti,
L.F.Lloyd,
D.Maeder,
A.Mistry,
P.Brick,
D.Blow,
D.M.Blow.
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Ref.
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J Mol Biol, 1989,
210,
241-242.
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PubMed id
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