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PDBsum entry 1id5
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Contents |
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30 a.a.
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256 a.a.
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138 a.a.
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* Residue conservation analysis
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PDB id:
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Hydrolase
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Title:
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Crystal structure of bovine thrombin complex with protease inhibitor ecotin
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Structure:
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Thrombin. Chain: l. Fragment: thrombin light chain. Thrombin. Chain: h. Fragment: thrombin heavy chain. Ecotin. Chain: i. Engineered: yes.
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Source:
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Bos taurus. Cattle. Organism_taxid: 9913. Escherichia coli. Organism_taxid: 562. Expressed in: escherichia coli. Expression_system_taxid: 562
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Biol. unit:
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Dimer (from PDB file)
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Resolution:
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2.50Å
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R-factor:
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0.203
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R-free:
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0.264
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Authors:
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S.X.Wang,R.J.Fletterick
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Key ref:
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S.X.Wang
et al.
(2001).
Crystal structure of thrombin-ecotin reveals conformational changes and extended interactions.
Biochemistry,
40,
10038-10046.
PubMed id:
DOI:
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Date:
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03-Apr-01
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Release date:
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05-Sep-01
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PROCHECK
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Headers
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References
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P00735
(THRB_BOVIN) -
Prothrombin from Bos taurus
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Seq:
Struc:
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625 a.a.
30 a.a.
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Enzyme class:
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Chains L, H:
E.C.3.4.21.5
- thrombin.
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Reaction:
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Preferential cleavage: Arg-|-Gly; activates fibrinogen to fibrin and releases fibrinopeptide A and B.
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DOI no:
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Biochemistry
40:10038-10046
(2001)
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PubMed id:
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Crystal structure of thrombin-ecotin reveals conformational changes and extended interactions.
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S.X.Wang,
C.T.Esmon,
R.J.Fletterick.
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ABSTRACT
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The protease inhibitor ecotin fails to inhibit thrombin despite its broad
specificity against serine proteases. A point mutation (M84R) in ecotin results
in a 1.5 nM affinity for thrombin, 10(4) times stronger than that of wild-type
ecotin. The crystal structure of bovine thrombin is determined in complex with
ecotin M84R mutant at 2.5 A resolution. Surface loops surrounding the active
site cleft of thrombin have undergone significant structural changes to permit
inhibitor binding. Particularly, the insertion loops at residues 60 and 148 in
thrombin, which likely mediate the interactions with macromolecules, are
displaced when the complex forms. Thrombin and ecotin M84R interact in two
distinct surfaces. The loop at residue 99 and the C-terminus of thrombin contact
ecotin through mixed polar and nonpolar interactions. The active site of
thrombin is filled with eight consecutive amino acids of ecotin and demonstrates
thrombin's preference for specific features that are compatible with the
thrombin cleavage site: negatively
charged-Pro-Val-X-Pro-Arg-hydrophobic-positively charged (P1 Arg is in bold
letters). The preference for a Val at P4 is clearly defined. The insertion at
residue 60 may further affect substrate binding by moving its adjacent loops
that are part of the substrate recognition sites.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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A.A.Stoop,
R.V.Joshi,
C.T.Eggers,
and
C.S.Craik
(2010).
Analysis of an engineered plasma kallikrein inhibitor and its effect on contact activation.
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Biol Chem,
391,
425-433.
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H.L.de Amorim,
P.A.Netz,
and
J.A.Guimarães
(2010).
Thrombin allosteric modulation revisited: a molecular dynamics study.
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J Mol Model,
16,
725-735.
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H.C.Castro,
R.Q.Monteiro,
M.Assafim,
N.I.Loureiro,
C.Craik,
and
R.B.Zingali
(2006).
Ecotin modulates thrombin activity through exosite-2 interactions.
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Int J Biochem Cell Biol,
38,
1893-1900.
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L.Jin,
P.Pandey,
R.E.Babine,
J.C.Gorga,
K.J.Seidl,
E.Gelfand,
D.T.Weaver,
S.S.Abdel-Meguid,
and
J.E.Strickler
(2005).
Crystal structures of the FXIa catalytic domain in complex with ecotin mutants reveal substrate-like interactions.
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J Biol Chem,
280,
4704-4712.
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PDB codes:
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J.K.Bell,
D.H.Goetz,
S.Mahrus,
J.L.Harris,
R.J.Fletterick,
and
C.S.Craik
(2003).
The oligomeric structure of human granzyme A is a determinant of its extended substrate specificity.
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Nat Struct Biol,
10,
527-534.
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PDB code:
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S.X.Wang,
E.Hur,
C.A.Sousa,
L.Brinen,
E.J.Slivka,
and
R.J.Fletterick
(2003).
The extended interactions and Gla domain of blood coagulation factor Xa.
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Biochemistry,
42,
7959-7966.
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PDB code:
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
codes are
shown on the right.
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Links
