1COU
ANTICOAGULANT PROTEIN FROM THE NEMATODE ANCYLOSTOMA CANINUM
Summary for 1COU
| Entry DOI | 10.2210/pdb1cou/pdb |
| NMR Information | BMRB: 4396 |
| Descriptor | PROTEIN (NEMATODE ANTICOAGULANT PROTEIN C2) (1 entity in total) |
| Functional Keywords | anticoagulant, protease inhibitor, blood clotting |
| Biological source | Ancylostoma caninum (dog hookworm) |
| Total number of polymer chains | 1 |
| Total formula weight | 9757.72 |
| Authors | Duggan, B.M.,Dyson, H.J.,Wright, P.E. (deposition date: 1999-05-28, release date: 1999-10-20, Last modification date: 2024-11-06) |
| Primary citation | Duggan, B.M.,Dyson, H.J.,Wright, P.E. Inherent flexibility in a potent inhibitor of blood coagulation, recombinant nematode anticoagulant protein c2. Eur.J.Biochem., 265:539-548, 1999 Cited by PubMed Abstract: Nematode anticoagulant proteins (NAPs) from the hematophagous nematode Ancylostoma caninum inhibit blood coagulation with picomolar inhibition constants, and have been targeted as novel pharmaceutical agents. NAP5 and NAP6 inhibit factor Xa by binding to its active site, whereas NAPc2 binds to factor Xa at a different, as yet unidentified, site and the resultant binary complex inhibits the tissue factor-factor VIIa complex. We have undertaken NMR studies of NAPc2, including the calculation of a solution structure, and found that the protein is folded, with five disulfide bonds, but is extremely flexible, especially in the acidic loop. The Halpha secondary shifts and 3JHNHalpha coupling constants indicate the presence of some beta structure and a short helix, but the intervening loops are highly conformationally heterogeneous. Heteronuclear NOE measurements showed the presence of large amplitude motions on a subnanosecond timescale at the N-terminus and C-terminus and in the substrate-binding loop, indicating that the conformational heterogeneity observed in the NMR structures is due to flexibility of the polypeptide chain in these regions. Flexibility may well be an important factor in the physiological function of NAPc2, because it must interact with other proteins in the inhibition of blood coagulation. We suggest that this inhibitor is likely to become structured on binding to factor Xa, because the inhibition of the tissue factor-factor VIIa complex requires both NAPc2 and factor Xa. PubMed: 10504384DOI: 10.1046/j.1432-1327.1999.00781.x PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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