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PDBsum entry 4bxw
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Blood clotting
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PDB id
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4bxw
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PDB id:
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| Name: |
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Blood clotting
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Title:
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Crystal structure of the prothrombinase complex from the venom of pseudonaja textilis
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Structure:
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Factor xa. Chain: a, b. Fragment: egf2-catalytic domain construct, residues 41-463. Engineered: yes. Other_details: pseutarin c catalytic subunit. Coagulation factor v. Chain: f. Fragment: a2 peptide, residues 693-710. Synonym: factor v a2 peptide.
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Source:
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Pseudonaja textilis. Australian eastern brown snake. Organism_taxid: 8673. Organ: venom gland. Expressed in: escherichia coli. Expression_system_taxid: 469008. Expression_system_variant: star. Synthetic: yes. Escherichia coli.
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Resolution:
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2.71Å
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R-factor:
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0.159
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R-free:
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0.233
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Authors:
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B.C.Lechtenberg,T.A.Murray-Rust,D.J.D.Johnson,T.E.Adams, S.Krishnaswamy,R.M.Camire,J.A.Huntington
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Key ref:
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B.C.Lechtenberg
et al.
(2013).
Crystal structure of the prothrombinase complex from the venom of Pseudonaja textilis.
Blood,
122,
2777-2783.
PubMed id:
DOI:
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Date:
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16-Jul-13
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Release date:
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31-Jul-13
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PROCHECK
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Headers
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References
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Q56VR3
(FAXC_PSETE) -
Venom prothrombin activator pseutarin-C catalytic subunit from Pseudonaja textilis
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Seq:
Struc:
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467 a.a.
286 a.a.*
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Key: |
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PfamA domain |
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Secondary structure |
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CATH domain |
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*
PDB and UniProt seqs differ
at 26 residue positions (black
crosses)
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Enzyme class:
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E.C.3.4.21.6
- coagulation factor Xa.
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Reaction:
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Preferential cleavage: Arg-|-Thr and then Arg-|-Ile bonds in prothrombin to form thrombin.
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DOI no:
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Blood
122:2777-2783
(2013)
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PubMed id:
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Crystal structure of the prothrombinase complex from the venom of Pseudonaja textilis.
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B.C.Lechtenberg,
T.A.Murray-Rust,
D.J.Johnson,
T.E.Adams,
S.Krishnaswamy,
R.M.Camire,
J.A.Huntington.
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ABSTRACT
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The prothrombinase complex, composed of the protease factor (f)Xa and cofactor
fVa, efficiently converts prothrombin to thrombin by specific sequential
cleavage at 2 sites. How the complex assembles and its mechanism of prothrombin
processing are of central importance to human health and disease, because
insufficient thrombin generation is the root cause of hemophilia, and excessive
thrombin production results in thrombosis. Efforts to determine the crystal
structure of the prothrombinase complex have been thwarted by the dependence of
complex formation on phospholipid membrane association. Pseutarin C is an
intrinsically stable prothrombinase complex preassembled in the venom gland of
the Australian Eastern Brown Snake (Pseudonaja textilis). Here we report the
crystal structures of the fX-fV complex and of activated fXa from P textilis
venom and the derived model of active pseutarin C. Structural analysis supports
a single substrate binding channel on fVa, to which prothrombin and the
intermediate meizothrombin bind in 2 different orientations, providing insight
into the architecture and mechanism of the prothrombinase complex-the molecular
engine of blood coagulation.
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Links
