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PDBsum entry 3uir
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Hydrolase/hydrolase inhibitor
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PDB id
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3uir
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References listed in PDB file
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Key reference
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Title
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The structure of human microplasmin in complex with textilinin-1, An aprotinin-Like inhibitor from the australian brown snake.
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Authors
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E.K.Millers,
L.A.Johnson,
G.W.Birrell,
P.P.Masci,
M.F.Lavin,
J.De jersey,
L.W.Guddat.
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Ref.
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Plos One, 2013,
8,
e54104.
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PubMed id
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Note In the PDB file this reference is
annotated as "TO BE PUBLISHED".
The citation details given above were identified by an automated
search of PubMed on title and author
names, giving a
percentage match of
96%.
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Abstract
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Textilinin-1 is a Kunitz-type serine protease inhibitor from Australian brown
snake venom. Its ability to potently and specifically inhibit human plasmin
(K(i) = 0.44 nM) makes it a potential therapeutic drug as a systemic
anti-bleeding agent. The crystal structures of the human
microplasmin-textilinin-1 and the trypsin-textilinin-1 complexes have been
determined to 2.78 Å and 1.64 Å resolution respectively, and show that
textilinin-1 binds to trypsin in a canonical mode but to microplasmin in an
atypical mode with the catalytic histidine of microplasmin rotated out of the
active site. The space vacated by the histidine side-chain in this complex is
partially occupied by a water molecule. In the structure of microplasminogen the
χ(1) dihedral angle of the side-chain of the catalytic histidine is rotated by
67° from its "active" position in the catalytic triad, as exemplified by its
location when microplasmin is bound to streptokinase. However, when textilinin-1
binds to microplasmin the χ(1) dihedral angle of this amino acid residue
changes by -157° (i.e. in the opposite rotation direction compared to
microplasminogen). The unusual mode of interaction between textilinin-1 and
plasmin explains textilinin-1's selectivity for human plasmin over plasma
kallikrein. This difference can be exploited in future drug design efforts.
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