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PDBsum entry 1kig
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Complex (protease/inhibitor)
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PDB id
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1kig
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Unexpected binding mode of tick anticoagulant peptide complexed to bovine factor xa.
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Authors
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A.Wei,
R.S.Alexander,
J.Duke,
H.Ross,
S.A.Rosenfeld,
C.H.Chang.
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Ref.
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J Mol Biol, 1998,
283,
147-154.
[DOI no: ]
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PubMed id
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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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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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