PDBsum entry 4bxs

Blood clotting

PDB id: 4bxs

Contents

Protein chains

248 a.a.

1262 a.a.

Ligands

NAG-FUC

NAG-NAG-BMA-MAN-MAN-MAN-MAN-MAN

NAG-NAG ×2

NAG

Metals

_CU

_CA ×2

Waters ×112

PDB id:

4bxs

Name:

Blood clotting

Title:

Crystal structure of the prothrombinase complex from the venom of pseudonaja textilis

Structure:

Factor x-like protease. Chain: a. Fragment: egf2-catalytic domain construct. Synonym: factor x. Engineered: yes. Other_details: pseutarin c catalytic subunit. Venom prothrombin activator pseutarin-c non-catalytic subunit. Chain: v.

Source:

Pseudonaja textilis. Australian eastern brown snake. Organism_taxid: 8673. Organ: venom gland. Expressed in: escherichia coli. Expression_system_taxid: 469008. Expression_system_variant: star. Expressed in: cricetulus griseus. Expression_system_taxid: 10029.

Resolution:

3.32Å R-factor: 0.301 R-free: 0.368

Authors:

B.C.Lechtenberg,T.A.Murray-Rust,D.J.D.Johnson,T.E.Adams, S.Krishnaswamy,R.M.Camire,J.A.Huntington

Key ref:

B.C.Lechtenberg et al. (2013). Crystal structure of the prothrombinase complex from the venom of Pseudonaja textilis. Blood, 122, 2777-2783. PubMed id: 23869089 DOI: 10.1182/blood-2013-06-511733

Date:

15-Jul-13 Release date: 31-Jul-13

Protein chain

Q56VR3  (FAXC_PSETE) -  Venom prothrombin activator pseutarin-C catalytic subunit from Pseudonaja textilis

Seq: 467 a.a.

Struc: 248 a.a.*

Protein chain

Q7SZN0  (FA5V_PSETE) -  Venom prothrombin activator pseutarin-C non-catalytic subunit from Pseudonaja textilis

Seq: 1460 a.a.

Struc: 1262 a.a.*

* PDB and UniProt seqs differ at 23 residue positions (black crosses)

Enzyme reactions

• Enzyme class: Chain A: E.C.3.4.21.6 - coagulation factor Xa.
• Reaction: Preferential cleavage: Arg-|-Thr and then Arg-|-Ile bonds in prothrombin to form thrombin.

DOI no: 10.1182/blood-2013-06-511733

Blood 122:2777-2783 (2013)

PubMed id: 23869089

Crystal structure of the prothrombinase complex from the venom of Pseudonaja textilis.

B.C.Lechtenberg, T.A.Murray-Rust, D.J.Johnson, T.E.Adams, S.Krishnaswamy, R.M.Camire, J.A.Huntington.

ABSTRACT

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.