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PDBsum entry 1fph
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Hydrolase/hydrolase inhibitor
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PDB id
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1fph
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Contents |
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36 a.a.
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259 a.a.
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12 a.a.
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12 a.a.
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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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The interaction of thrombin with fibrinogen. A structural basis for its specificity.
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Authors
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M.T.Stubbs,
H.Oschkinat,
I.Mayr,
R.Huber,
H.Angliker,
S.R.Stone,
W.Bode.
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Ref.
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Eur J Biochem, 1992,
206,
187-195.
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PubMed id
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Abstract
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The structure of the ternary complex of human alpha-thrombin with a covalently
bound analogue of fibrinopeptide A and a C-terminal hirudin peptide has been
determined by X-ray diffraction methods at 0.25 nm resolution. Fibrinopeptide A
folds in a compact manner, bringing together hydrophobic residues that slot into
the apolar binding site of human alpha-thrombin. Fibrinogen residue Phe8
occupies the aryl-binding site of thrombin, adjacent to fibrinogen residues Leu9
and Val15 in the S2 subsite. The species diversity of fibrinopeptide A is
analysed with respect to its conformation and its interaction with thrombin. The
non-covalently attached peptide fragment hirudin(54-65) exhibits an identical
conformation to that observed in the hirudin-thrombin complex. The occupancy of
the secondary fibrinogen-recognition exosite by this peptide imposes
restrictions on the manner of fibrinogen binding. The surface topology of the
thrombin molecule indicates positions P1'-P3', differ from those of the
canonical serine-proteinase inhibitors, suggesting a mechanical model for the
switching of thrombin activity from fibrinogen cleavage to protein-C activation
on thrombomodulin complex formation. The multiple interactions between thrombin
and fibrinogen provide an explanation for the narrow specificity of thrombin.
Structural grounds can be put forward for certain congenital clotting disorders.
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Secondary reference #1
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Title
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A player of many parts: the spotlight falls on thrombin'S structure.
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Authors
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M.T.Stubbs,
W.Bode.
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Ref.
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Thromb Res, 1993,
69,
1.
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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 X-Ray crystal structure of d-Phe-Pro-Arg chloromethylketone-Inhibited human alpha-Thrombin: structure analysis, Overall structure, Electrostatic properties, Detailed active-Site geometry, And structure-Function relationships.
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Authors
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W.Bode,
D.Turk,
A.Karshikov.
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Ref.
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Protein Sci, 1992,
1,
426-471.
[DOI no: ]
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PubMed id
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Figure 3.
Fig. 3. Tosyl-m-amidinophenylalanyl-piperidine (thickconnections), NAPAP (mediumconnections),and MQPA (thincon-
nections)boundtotheactivesite of humana-thrombindisplayedtogetherwiththeConnollysurface f thrombin(Turk et al.,
1991). The naphthyl/toluene/chinolyl groups of theinhibitorsinteractwiththearyl-bindingsiteofthrombin;thesidechains
ofthe m- and thep-amidinophenylalanyl residues andofthe arginylresidueenterthespecificitypocketfrom slightly differing
sites; the S2 subsiteofthrombin is occupiedtodifferentextentsbythe(partiallysubstituted)piperidinemoieties.The viewis
similartothestandard view of Figure .
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Figure 30.
Fig. 30. Luzzatiplot f thefinalthrombinmodelafterX-PLOR
refinement.
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The above figures are
reproduced from the cited reference
with permission from the Protein Society
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Secondary reference #3
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Title
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Refined structure of the hirudin-Thrombin complex.
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Authors
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T.J.Rydel,
A.Tulinsky,
W.Bode,
R.Huber.
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Ref.
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J Mol Biol, 1991,
221,
583-601.
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PubMed id
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