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PDBsum entry 1de7
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Hydrolase/hydrolase substrate
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PDB id
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1de7
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Contents |
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28 a.a.
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249 a.a.
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26 a.a.
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11 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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Interaction of the factor xiii activation peptide with alpha -Thrombin. Crystal structure of its enzyme-Substrate analog complex.
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Authors
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C.Sadasivan,
V.C.Yee.
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Ref.
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J Biol Chem, 2000,
275,
36942-36948.
[DOI no: ]
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PubMed id
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Abstract
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The serine protease thrombin proteolytically activates blood coagulation factor
XIII by cleavage at residue Arg(37); factor XIII in turn cross-links fibrin
molecules and gives mechanical stability to the blood clot. The 2.0-A resolution
x-ray crystal structure of human alpha-thrombin bound to the factor XIII-(28-37)
decapeptide has been determined. This structure reveals the detailed atomic
level interactions between the factor XIII activation peptide and thrombin and
provides the first high resolution view of this functionally important part of
the factor XIII molecule. A comparison of this structure with the crystal
structure of fibrinopeptide A complexed with thrombin highlights several
important determinants of thrombin substrate interaction. First, the P1 and P2
residues must be compatible with the geometry and chemistry of the S1 and S2
specificity sites in thrombin. Second, a glycine in the P5 position is necessary
for the conserved substrate conformation seen in both factor XIII-(28-37) and
fibrinopeptide A. Finally, the hydrophobic residues, which occupy the aryl
binding site of thrombin determine the substrate conformation further away from
the catalytic residues. In the case of factor XIII-(28-37), the aryl binding
site is shared by hydrophobic residues P4 (Val(34)) and P9 (Val(29)). A bulkier
residue in either of these sites may alter the substrate peptide conformation.
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Figure 3.
Fig. 3. Schematic representation of van der Waals
interactions (  4 Å) of
thrombin with fXIII -(28-37) PEP1 (top) and FPA (15) (bottom).
Interactions with the underlined residues are observed only in
the given complex.
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Figure 6.
Fig. 6. Superposition of Val34 in fXIII -(28-37) and
surrounding thrombin residues. (PEP1, red; PEP2, green; FPA,
blue; PPACK, magenta). The presence of the Val34 side chain in
fXIII-(28-37) makes a shift in surrounding thrombin residues.
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2000,
275,
36942-36948)
copyright 2000.
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Secondary reference #1
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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 #2
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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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Secondary reference #3
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Title
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Three-Dimensional structure of a transglutaminase: human blood coagulation factor xiii.
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Authors
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V.C.Yee,
L.C.Pedersen,
I.Le trong,
P.D.Bishop,
R.E.Stenkamp,
D.C.Teller.
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Ref.
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Proc Natl Acad Sci U S A, 1994,
91,
7296-7300.
[DOI no: ]
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PubMed id
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