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PDBsum entry 1g3d
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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X-Ray crystallographic analyses of complexes between bovine beta-Trypsin and schiff base copper(ii) or iron(III) chelates.
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Authors
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E.Toyota,
K.K.Ng,
H.Sekizaki,
K.Itoh,
K.Tanizawa,
M.N.James.
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Ref.
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J Mol Biol, 2001,
305,
471-479.
[DOI no: ]
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PubMed id
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Abstract
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To establish the structural basis underlying the activity of a novel series of
metal-chelate trypsin inhibitors, the structures of
p-amidinosalicylidene-l-alaninato(aqua)copper(II) (1a),
m-amidinosalicylidene-l-alaninato(aqua)copper(II) (1b),
bis(p-amidinosalicylidene-l-alaninato)iron(III) (2a), and
bis(m-amidinosalicylidene-l-alaninato)iron(III) (2b) bound to bovine
beta-trypsin were studied by X-ray crystallography. The amidinium group of the
inhibitor donates hydrogen bonds to Asp189, Gly219 and Ser190, as seen before in
trypsin-benzamidine complexes. The copper(II) ion of 1a is situated away from
trypsin's catalytic triad residues, and is octahedrally coordinated by a Schiff
base and three water molecules. In contrast, the copper(II) ion of 1b is
situated close to the catalytic triad and adopts a square pyramidal coordination
geometry. The iron(III) ion of 2a is octahedrally coordinated by two Schiff base
ligands and, like the copper(II) ion of 1a, is situated away from the catalytic
triad. The p-amidinophenyl ring of a second Schiff base ligand of 2a is directed
toward a hydrophobic groove formed by Trp215 and Leu99. Finally, the iron(III)
ion of 2b appears to be replaced by magnesium(II), which is octahedrally
coordinated by a Schiff base, Gln192 and two water molecules. One of the Schiff
base ligands seen in the trypsin-2a complex or in the unbound form of 2b is
replaced by water molecules and Gln192. His57 and Ser195 form water-mediated
interactions with the magnesium(II) ion of 2b, and Ser195 also forms a hydrogen
bond with the phenolic oxygen atom of the Schiff base ligand. These structures
reveal a novel mode of interaction between metal-chelate inhibitors and serine
proteases, thus providing a structural basis for the development of more potent
inhibitors against a variety of trypsin-like enzymes.
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Figure 1.
Figure 1. Chemical formulae of the inhibitors used in this
study.
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Figure 3.
Figure 3. Schematic representation of metal coordination
geometry and hydrogen bonds of trypsin-1a (a), trypsin-1b (b),
trypsin-2a (c) and trypsin-2b (d) complexes in the region of
active site. Hydrogen bonds between inhibitor and trypsin are
drawn in broken lines.
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The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(2001,
305,
471-479)
copyright 2001.
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