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PDBsum entry 1toc
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Complex (hydrolase/inhibitor)
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PDB id
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1toc
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Contents |
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28 a.a.
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259 a.a.
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120 a.a.
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References listed in PDB file
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Key reference
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Title
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The ornithodorin-Thrombin crystal structure, A key to the tap enigma?
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Authors
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A.Van de locht,
M.T.Stubbs,
W.Bode,
T.Friedrich,
C.Bollschweiler,
W.Höffken,
R.Huber.
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Ref.
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Embo J, 1996,
15,
6011-6017.
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PubMed id
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Abstract
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Ornithodorin, isolated from the blood sucking soft tick Ornithodoros moubata, is
a potent (Ki = 10(-12) M) and highly selective thrombin inhibitor. Internal
sequence homology indicates a two domain protein. Each domain resembles the
Kunitz inhibitor basic pancreatic trypsin inhibitor (BPTI) and also the tick
anticoagulant peptide (TAP) isolated from the same organism. The 3.1 A crystal
structure of the ornithodorin-thrombin complex confirms that both domains of
ornithodorin exhibit a distorted BPTI-like fold. The N-terminal portion and the
C-terminal helix of each domain are structurally very similar to BPTI, whereas
the regions corresponding to the binding loop of BPTI adopt different
conformations. Neither of the two 'reactive site loops' of ornithodorin contacts
the protease in the ornithodorin-thrombin complex. Instead, the N-terminal
residues of ornithodorin bind to the active site of thrombin, reminiscent of the
thrombin-hirudin interaction. The C-terminal domain binds at the fibrinogen
recognition exosite. Molecular recognition of its target protease by this
double-headed Kunitz-type inhibitor diverges considerably from other members of
this intensely studied superfamily. The complex structure provides a model to
explain the perplexing results of mutagenesis studies on the TAP-factor Xa
interaction.
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Secondary reference #1
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Title
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Two heads are better than one: crystal structure of the insect derived double domain kazal inhibitor rhodniin in complex with thrombin.
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Authors
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A.Van de locht,
D.Lamba,
M.Bauer,
R.Huber,
T.Friedrich,
B.Kröger,
W.Höffken,
W.Bode.
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Ref.
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Embo J, 1995,
14,
5149-5157.
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PubMed id
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Secondary reference #2
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Title
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The refined 1.9 a crystal structure of human alpha-Thrombin: interaction with d-Phe-Pro-Arg chloromethylketone and significance of the tyr-Pro-Pro-Trp insertion segment.
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Authors
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W.Bode,
I.Mayr,
U.Baumann,
R.Huber,
S.R.Stone,
J.Hofsteenge.
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Ref.
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Embo J, 1989,
8,
3467-3475.
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PubMed id
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