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PDBsum entry 3e1x
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Contents |
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* Residue conservation analysis
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Protein Sci
18:1081-1094
(2009)
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PubMed id:
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Active site conformational changes of prostasin provide a new mechanism of protease regulation by divalent cations.
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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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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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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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A.Sukhwal,
M.Bhattacharyya,
and
S.Vishveshwara
(2011).
Network approach for capturing ligand-induced subtle global changes in protein structures.
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Acta Crystallogr D Biol Crystallogr,
67,
429-439.
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A.D.Vogt,
A.Bah,
and
E.Di Cera
(2010).
Evidence of the E*-E equilibrium from rapid kinetics of Na+ binding to activated protein C and factor Xa.
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J Phys Chem B,
114,
16125-16130.
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C.Eigenbrot,
R.Ganesan,
and
D.Kirchhofer
(2010).
Hepatocyte growth factor activator (HGFA): molecular structure and interactions with HGFA inhibitor-1 (HAI-1).
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FEBS J,
277,
2215-2222.
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T.M.Antalis,
M.S.Buzza,
K.M.Hodge,
J.D.Hooper,
and
S.Netzel-Arnett
(2010).
The cutting edge: membrane-anchored serine protease activities in the pericellular microenvironment.
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Biochem J,
428,
325-346.
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Z.Chen,
L.A.Pelc,
and
E.Di Cera
(2010).
Crystal structure of prethrombin-1.
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Proc Natl Acad Sci U S A,
107,
19278-19283.
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PDB code:
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P.S.Gandhi,
M.J.Page,
Z.Chen,
L.Bush-Pelc,
and
E.Di Cera
(2009).
Mechanism of the anticoagulant activity of thrombin mutant W215A/E217A.
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J Biol Chem,
284,
24098-24105.
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PDB codes:
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R.Ganesan,
C.Eigenbrot,
Y.Wu,
W.C.Liang,
S.Shia,
M.T.Lipari,
and
D.Kirchhofer
(2009).
Unraveling the allosteric mechanism of serine protease inhibition by an antibody.
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Structure,
17,
1614-1624.
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PDB codes:
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
code is
shown on the right.
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Links
