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PDBsum entry 3ib0
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Metal binding protein
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PDB id
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3ib0
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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 structural basis for the prevention of nonsteroidal antiinflammatory drug-Induced gastrointestinal tract damage by the c-Lobe of bovine colostrum lactoferrin.
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Authors
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R.Mir,
N.Singh,
G.Vikram,
R.P.Kumar,
M.Sinha,
A.Bhushan,
P.Kaur,
A.Srinivasan,
S.Sharma,
T.P.Singh.
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Ref.
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Biophys J, 2009,
97,
3178-3186.
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PubMed id
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Abstract
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Nonsteroidal antiinflammatory drugs (NSAIDs), due to their good efficacy in the
treatment of pain, inflammation, and fever, are among the most prescribed class
of medicines in the world. The main drawback of NSAIDs is that they induce
gastric complications such as peptic ulceration and injury to the intestine.
Four NSAIDs, indomethacin, diclofenac, aspirin, and ibuprofen were selected to
induce gastropathy in mouse models. It was found that the addition of C-terminal
half of bovine lactoferrin (C-lobe) reversed the NSAID-induced injuries to the
extent of 47-70% whereas the coadministration of C-lobe prevented it
significantly. The C-lobe was prepared proteolytically using serine proteases.
The binding studies of C-lobe with NSAIDs showed that these compounds bind to
C-lobe with affinities ranging from 2.6 to 4.8 x 10(-4) M. The complexes of
C-lobe were prepared with the above four NSAIDs. All four complexes were
crystallized and their detailed three-dimensional structures were determined
using x-ray crystallographic method. The structures showed that all the four
NSAID molecules bound to C-lobe at the newly identified ligand binding site in
C-lobe that is formed involving two alpha-helices, alpha10 and alpha11. The
ligand binding site is separated from the well known iron binding site by the
longest and the most stable beta-strand, betaj, in the structure. Similar
results were also obtained with the full length lactoferrin molecule. This
novel, to our knowledge, binding site in C-lobe of lactoferrin shows a good
complementarity for the acidic and lipophilic compounds such as NSAIDs. We
believe this indicates that C-lobe of lactoferrin can be exploited for the
prevention of NSAID-induced gastropathy.
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