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* Residue conservation analysis
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PDB id:
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Complex (protease/inhibitor)
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Title:
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Bovine factor xa
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Structure:
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Factor xa. Chain: h. Engineered: yes. Factor xa. Chain: l. Engineered: yes. Anticoagulant peptide. Chain: i. Synonym: rtap.
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Source:
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Bos taurus. Cattle. Organism_taxid: 9913. Organ: blood. Expressed in: saccharomyces cerevisiae. Expression_system_taxid: 4932. Ornithodoros moubata. Organism_taxid: 6938. Expression_system_taxid: 4932
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Biol. unit:
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Trimer (from
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Resolution:
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Authors:
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A.Wei,R.Alexander,C.-H.Chang
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Key ref:
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A.Wei
et al.
(1998).
Unexpected binding mode of tick anticoagulant peptide complexed to bovine factor Xa.
J Mol Biol,
283,
147-154.
PubMed id:
DOI:
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Date:
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24-Apr-97
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Release date:
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28-Oct-98
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PROCHECK
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Headers
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References
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P00743
(FA10_BOVIN) -
Coagulation factor X from Bos taurus
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Seq:
Struc:
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492 a.a.
241 a.a.
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Enzyme class:
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Chains H, L:
E.C.3.4.21.6
- coagulation factor Xa.
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Reaction:
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Preferential cleavage: Arg-|-Thr and then Arg-|-Ile bonds in prothrombin to form thrombin.
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DOI no:
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J Mol Biol
283:147-154
(1998)
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PubMed id:
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Unexpected binding mode of tick anticoagulant peptide complexed to bovine factor Xa.
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A.Wei,
R.S.Alexander,
J.Duke,
H.Ross,
S.A.Rosenfeld,
C.H.Chang.
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ABSTRACT
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The structure of recombinant tick anticoagulant peptide (rTAP) complexed to
bovine factor Xa at 3.0 A resolution reveals the structural basis for the
specificity and the high affinity of rTAP. Three N-terminal residues, Tyr501,
Asn502 and Arg503, play a critical role in the complex formation as suggested by
earlier mutagenic studies and the ornithodorin-thrombin complex. Unexpectedly,
the side-chain of Tyr501 is located in the S1 pocket, although factor Xa favors
arginine as a P1 residue. Arg503 is located at the aryl binding pocket and forms
a salt-bridge with Glu97 of factor Xa. The autolysis loop, which is disordered
in the uninhibited factor Xa structure, is involved in the formation of the
complex as a part of the secondary binding site. The C-terminal helix of rTAP
interacts with factor Xa as a secondary binding determinant. The N-terminal
residues of rTAP reorganize during the formation of the factor Xa-rTAP complex
from the conformation found in the solution into an extended conformation. The
presence of the secondary binding site confirms the proposed two-step kinetic
mechanism based on the results of a mutagenesis study.
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Selected figure(s)
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Figure 2.
Figure 2. Stereo view of the (F[o] -F[c]) electron density
map around the N-terminal residue Tyr501. The N terminus (Tyr501
to Arg503) of rTAP (yellow) is locked into the active site of
factor Xa (atom type) to form a complex with rTAP. The phases
were calculated without the coordinates of the first three
N-terminal residues of rTAP. The electron density map was
contoured at 2.5 s.
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Figure 4.
Figure 4. Superposition of thrombin (cyan)-ornithodorin
(yellow, N-terminal domain shown) complex on the coordinates of
the factor Xa (green)-rTAP (red) complex. Although the use of
alpha-helix and the N-terminal amino acid residues is conserved
between these two proteins, the orientation of these groups is
different in each structure.
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The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(1998,
283,
147-154)
copyright 1998.
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Figures were
selected
by an automated process.
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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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B.G.Fry,
K.Roelants,
D.E.Champagne,
H.Scheib,
J.D.Tyndall,
G.F.King,
T.J.Nevalainen,
J.A.Norman,
R.J.Lewis,
R.S.Norton,
C.Renjifo,
and
R.C.de la Vega
(2009).
The toxicogenomic multiverse: convergent recruitment of proteins into animal venoms.
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Annu Rev Genomics Hum Genet,
10,
483-511.
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R.Chattopadhyay,
R.Iacob,
S.Sen,
R.Majumder,
K.B.Tomer,
and
B.R.Lentz
(2009).
Functional and structural characterization of factor Xa dimer in solution.
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Biophys J,
96,
974-986.
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C.Y.Koh,
and
R.M.Kini
(2008).
Anticoagulants from hematophagous animals.
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Expert Rev Hematol,
1,
135-139.
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H.J.Hsu,
K.C.Tsai,
Y.K.Sun,
H.J.Chang,
Y.J.Huang,
H.M.Yu,
C.H.Lin,
S.S.Mao,
and
A.S.Yang
(2008).
Factor Xa active site substrate specificity with substrate phage display and computational molecular modeling.
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J Biol Chem,
283,
12343-12353.
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L.Yang,
C.Manithody,
S.H.Qureshi,
and
A.R.Rezaie
(2008).
Factor Va alters the conformation of the Na+-binding loop of factor Xa in the prothrombinase complex.
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Biochemistry,
47,
5976-5985.
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R.Toso,
H.Zhu,
and
R.M.Camire
(2008).
The conformational switch from the factor X zymogen to protease state mediates exosite expression and prothrombinase assembly.
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J Biol Chem,
283,
18627-18635.
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S.Macedo-Ribeiro,
C.Almeida,
B.M.Calisto,
T.Friedrich,
R.Mentele,
J.Stürzebecher,
P.Fuentes-Prior,
and
P.J.Pereira
(2008).
Isolation, cloning and structural characterisation of boophilin, a multifunctional Kunitz-type proteinase inhibitor from the cattle tick.
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PLoS ONE,
3,
e1624.
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PDB code:
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J.Otlewski,
F.Jelen,
M.Zakrzewska,
and
A.Oleksy
(2005).
The many faces of protease-protein inhibitor interaction.
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EMBO J,
24,
1303-1310.
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M.A.Bukys,
M.A.Blum,
P.Y.Kim,
N.Brufatto,
M.E.Nesheim,
and
M.Kalafatis
(2005).
Incorporation of factor Va into prothrombinase is required for coordinated cleavage of prothrombin by factor Xa.
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J Biol Chem,
280,
27393-27401.
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W.Bode
(2005).
The structure of thrombin, a chameleon-like proteinase.
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J Thromb Haemost,
3,
2379-2388.
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A.R.Rezaie,
and
F.S.Kittur
(2004).
The critical role of the 185-189-loop in the factor Xa interaction with Na+ and factor Va in the prothrombinase complex.
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J Biol Chem,
279,
48262-48269.
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G.Izaguirre,
W.Zhang,
R.Swanson,
T.Bedsted,
and
S.T.Olson
(2003).
Localization of an antithrombin exosite that promotes rapid inhibition of factors Xa and IXa dependent on heparin activation of the serpin.
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J Biol Chem,
278,
51433-51440.
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J.P.Ludeman,
R.N.Pike,
K.M.Bromfield,
P.J.Duggan,
J.Cianci,
B.Le Bonniec,
J.C.Whisstock,
and
S.P.Bottomley
(2003).
Determination of the P1', P2' and P3' subsite-specificity of factor Xa.
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Int J Biochem Cell Biol,
35,
221-225.
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C.Manithody,
L.Yang,
and
A.R.Rezaie
(2002).
Role of basic residues of the autolysis loop in the catalytic function of factor Xa.
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Biochemistry,
41,
6780-6788.
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M.Wilkens,
and
S.Krishnaswamy
(2002).
The contribution of factor Xa to exosite-dependent substrate recognition by prothrombinase.
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J Biol Chem,
277,
9366-9374.
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M.Adler,
D.D.Davey,
G.B.Phillips,
S.H.Kim,
J.Jancarik,
G.Rumennik,
D.R.Light,
and
M.Whitlow
(2000).
Preparation, characterization, and the crystal structure of the inhibitor ZK-807834 (CI-1031) complexed with factor Xa.
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Biochemistry,
39,
12534-12542.
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PDB code:
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R.St Charles,
K.Padmanabhan,
R.V.Arni,
K.P.Padmanabhan,
and
A.Tulinsky
(2000).
Structure of tick anticoagulant peptide at 1.6 A resolution complexed with bovine pancreatic trypsin inhibitor.
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Protein Sci,
9,
265-272.
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PDB code:
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A.Wei,
A.Smallwood,
R.S.Alexander,
J.Duke,
H.Ross,
S.A.Rosenfeld,
and
C.H.Chang
(1999).
Crystallization and preliminary X-ray diffraction data of the complex of recombinant tick anticoagulant peptide (rTAP) and bovine factor Xa.
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Acta Crystallogr D Biol Crystallogr,
55,
862-864.
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U.Sinha
(1999).
Synthetic inhibitors of coagulation factor Xa.
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Expert Opin Investig Drugs,
8,
567-573.
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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
