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PDBsum entry 1tbr
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Complex (serine protease/inhibitor)
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PDB id
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1tbr
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Contents |
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49 a.a.
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259 a.a.
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103 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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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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Abstract
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Rhodniin is a highly specific inhibitor of thrombin isolated from the assassin
bug Rhodnius prolixus. The 2.6 Angstrum crystal structure of the non-covalent
complex between recombinant rhodniin and bovine alpha-thrombin reveals that the
two Kazal-type domains of rhodniin bind to different sites of thrombin. The
amino-terminal domain binds in a substrate-like manner to the narrow active-site
cleft of thrombin; the imidazole group of the P1 His residue extends into the S1
pocket to form favourable hydrogen/ionic bonds with Asp189 at its bottom, and
additionally with Glu192 at its entrance. The carboxy-terminal domain, whose
distorted reactive-site loop cannot adopt the canonical conformation, docks to
the fibrinogen recognition exosite via extensive electrostatic interactions. The
rather acidic polypeptide linking the two domains is displaced from the thrombin
surface, with none of its residues involved in direct salt bridges with
thrombin. The tight (Ki = 2 x 10(-13) M) binding of rhodniin to thrombin is the
result of the sum of steric and charge complementarity of the amino-terminal
domain towards the active-site cleft, and of the electrostatic interactions
between the carboxy-terminal domain and the exosite.
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Secondary reference #1
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Title
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A kazal-Type inhibitor with thrombin specificity from rhodnius prolixus.
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Authors
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T.Friedrich,
B.Kröger,
S.Bialojan,
H.G.Lemaire,
H.W.Höffken,
P.Reuschenbach,
M.Otte,
J.Dodt.
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Ref.
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J Biol Chem, 1993,
268,
16216-16222.
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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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Secondary reference #4
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Title
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Crystal structure of the thrombin-Hirudin complex: a novel mode of serine protease inhibition.
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Authors
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M.G.Grütter,
J.P.Priestle,
J.Rahuel,
H.Grossenbacher,
W.Bode,
J.Hofsteenge,
S.R.Stone.
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Ref.
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Embo J, 1990,
9,
2361-2365.
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PubMed id
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Secondary reference #5
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Title
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The structure of a complex of recombinant hirudin and human alpha-Thrombin.
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Authors
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T.J.Rydel,
K.G.Ravichandran,
A.Tulinsky,
W.Bode,
R.Huber,
C.Roitsch,
J.W.Fenton.
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Ref.
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Science, 1990,
249,
277-280.
[DOI no: ]
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PubMed id
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Secondary reference #6
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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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