 |
PDBsum entry 1ny2
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Hydrolase/hydrolase inhibitor
|
PDB id
|
|
|
|
1ny2
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
Contents |
 |
|
|
|
|
|
|
|
|
|
|
|
|
* Residue conservation analysis
|
|
|
|
|
|
|
|
|
|
Enzyme class:
|
|
Chains 1, 2:
E.C.3.4.21.5
- thrombin.
|
|
|
|
|
|
|
Reaction:
|
|
Preferential cleavage: Arg-|-Gly; activates fibrinogen to fibrin and releases fibrinopeptide A and B.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
| |
|
|
Am J Physiol Heart Circ Physiol
285:H183
(2003)
|
|
PubMed id:
|
|
|
|
|
|
| |
|
Mechanisms of Arg-Pro-Pro-Gly-Phe inhibition of thrombin.
|
|
A.A.Hasan,
M.Warnock,
M.Nieman,
S.Srikanth,
F.Mahdi,
R.Krishnan,
A.Tulinsky,
A.H.Schmaier.
|
|
|
|
|
| |
ABSTRACT
|
|
|
|
| |
|
|
Investigations determined the mechanism(s) by which Arg-Pro-Pro-Gly-Phe (RPPGF)
inhibits thrombin-induced platelet activation. High concentrations of RPPGF
inhibit thrombin-induced coagulant activity. RPPGF binds to the active site of
thrombin by forming a parallel beta-strand with Ser214-Gly216 and interacts with
His57, Asp189, and Ser195 of the catalytic triad. RPPGF competitively inhibits
alpha-thrombin from hydrolyzing Sar-Pro-Arg-paranitroanilide with a Ki = 1.75
+/- 0.03 mM. Other mechanisms were sought to explain why RPPGF inhibits thrombin
activation of platelets at concentrations below that which inhibits its active
site. Soluble RPPGF blocks biotinylated NATLDPRSFLLR of the thrombin cleavage
site on protease-activated receptor (PAR)1 from binding to the peptide RPPGC
(IC50 = 20 microM). The soluble recombinant extracellular domain of PAR1
(rPAR1EC) blocks biotinylated RPPGF binding to rPAR1EC (IC50 = 50 microM) bound
to microtiter plates, but rPAR1EC deletion mutants missing the sequence LDPR or
PRSF do not. RPPGF and related forms prevent the thrombin-like enzyme
thrombocytin from proteolyzing rPAR1EC at concentrations that do not block
thrombocytin's active site. These studies indicate that RPPGF is a bifunctional
inhibitor of thrombin: it binds to PAR1 to prevent thrombin cleavage at Arg41
and interacts with the active site of alpha-thrombin.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
 |
 |
|
Literature references that cite this PDB file's key reference
|
|
|
| |
PubMed id
|
|
Reference
|
|
|
|
|
|
A.M.Marney,
J.Ma,
J.M.Luther,
T.A.Ikizler,
and
N.J.Brown
(2009).
Endogenous bradykinin contributes to increased plasminogen activator inhibitor 1 antigen following hemodialysis.
|
| |
J Am Soc Nephrol,
20,
2246-2252.
|
|
|
|
|
|
|
M.T.Nieman,
F.Burke,
M.Warnock,
Y.Zhou,
J.Sweigart,
A.Chen,
D.Ricketts,
B.R.Lucchesi,
Z.Chen,
E.Di Cera,
J.Hilfinger,
J.S.Kim,
H.I.Mosberg,
and
A.H.Schmaier
(2008).
Thrombostatin FM compounds: direct thrombin inhibitors - mechanism of action in vitro and in vivo.
|
| |
J Thromb Haemost,
6,
837-845.
|
|
|
PDB code:
|
|
|
|
|
|
|
|
F.M.Burke,
M.Warnock,
A.H.Schmaier,
and
H.I.Mosberg
(2006).
Synthesis of novel peptide inhibitors of thrombin-induced platelet activation.
|
| |
Chem Biol Drug Des,
68,
235-238.
|
|
|
|
|
|
|
Z.Shariat-Madar,
F.Mahdi,
M.Warnock,
J.W.Homeister,
S.Srikanth,
Y.Krijanovski,
L.J.Murphey,
A.A.Jaffa,
and
A.H.Schmaier
(2006).
Bradykinin B2 receptor knockout mice are protected from thrombosis by increased nitric oxide and prostacyclin.
|
| |
Blood,
108,
192-199.
|
|
|
|
|
|
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.
|
|
|
Links
