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PDBsum entry 1twx
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Hydrolase/hydrolase inhibitor
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PDB id
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1twx
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Contents |
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* Residue conservation analysis
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Enzyme class:
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Chains A, B:
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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Biophys Chem
112:253-256
(2004)
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PubMed id:
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Crystal structure of the thrombin mutant D221A/D222K: the Asp222:Arg187 ion-pair stabilizes the fast form.
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A.O.Pineda,
E.Zhang,
E.R.Guinto,
S.N.Savvides,
A.Tulinsky,
E.Di Cera.
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ABSTRACT
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The thrombin mutant D221A/D222K (ARK) does not bind Na+ and has interesting
functional properties intermediate between those of the slow and fast forms of
wild type. We solved the X-ray crystal structure of ARK bound at exosite I with
a fragment of hirudin at 2.4-A resolution. The structure shows a slight collapse
of the 186 and 220 loops into the Na+ binding site due to disruption of the
Asp222:Arg187 ion-pair. The backbone O atoms of Arg221a and Lys224 are shifted
into conformations that eliminate optimal interaction with Na+. A paucity of
solvent molecules in the Na+ binding site is also noted, by analogy to what is
seen in the structure of the slow form. These findings reinforce the crucial
role of the Asp222:Arg187 ion-pair in stabilizing the fast form of thrombin.
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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.D.Vogt,
A.Bah,
and
E.Di Cera
(2010).
Evidence of the E*-E equilibrium from rapid kinetics of Na+ binding to activated protein C and factor Xa.
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J Phys Chem B,
114,
16125-16130.
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E.Di Cera
(2008).
Thrombin.
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Mol Aspects Med,
29,
203-254.
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F.Marino,
Z.W.Chen,
C.E.Ergenekan,
L.A.Bush-Pelc,
F.S.Mathews,
and
E.Di Cera
(2007).
Structural basis of Na+ activation mimicry in murine thrombin.
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J Biol Chem,
282,
16355-16361.
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PDB codes:
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J.T.Crawley,
S.Zanardelli,
C.K.Chion,
and
D.A.Lane
(2007).
The central role of thrombin in hemostasis.
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J Thromb Haemost,
5,
95.
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L.A.Bush-Pelc,
F.Marino,
Z.Chen,
A.O.Pineda,
F.S.Mathews,
and
E.Di Cera
(2007).
Important role of the cys-191 cys-220 disulfide bond in thrombin function and allostery.
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J Biol Chem,
282,
27165-27170.
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PDB codes:
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L.A.Bush,
R.W.Nelson,
and
E.Di Cera
(2006).
Murine thrombin lacks Na+ activation but retains high catalytic activity.
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J Biol Chem,
281,
7183-7188.
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M.E.Papaconstantinou,
C.J.Carrell,
A.O.Pineda,
K.M.Bobofchak,
F.S.Mathews,
C.S.Flordellis,
M.E.Maragoudakis,
N.E.Tsopanoglou,
and
E.Di Cera
(2005).
Thrombin functions through its RGD sequence in a non-canonical conformation.
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J Biol Chem,
280,
29393-29396.
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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
