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PDBsum entry 3e1x
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References listed in PDB file
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Key reference
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Title
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Active site conformational changes of prostasin provide a new mechanism of protease regulation by divalent cations.
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Authors
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G.Spraggon,
M.Hornsby,
A.Shipway,
D.C.Tully,
B.Bursulaya,
H.Danahay,
J.L.Harris,
S.A.Lesley.
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Ref.
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Protein Sci, 2009,
18,
1081-1094.
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PubMed id
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Abstract
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Prostasin or human channel-activating protease 1 has been reported to play a
critical role in the regulation of extracellular sodium ion transport via its
activation of the epithelial cell sodium channel. Here, the structure of the
extracellular portion of the membrane associated serine protease has been solved
to high resolution in complex with a nonselective d-FFR chloromethyl ketone
inhibitor, in an apo form, in a form where the apo crystal has been soaked with
the covalent inhibitor camostat and in complex with the protein inhibitor
aprotinin. It was also crystallized in the presence of the divalent cation
Ca(+2). Comparison of the structures with each other and with other members of
the trypsin-like serine protease family reveals unique structural features of
prostasin and a large degree of conformational variation within specificity
determining loops. Of particular interest is the S1 subsite loop which opens and
closes in response to basic residues or divalent ions, directly binding Ca(+2)
cations. This induced fit active site provides a new possible mode of regulation
of trypsin-like proteases adapted in particular to extracellular regions with
variable ionic concentrations such as the outer membrane layer of the epithelial
cell.
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