1cou
From Proteopedia
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ANTICOAGULANT PROTEIN FROM THE NEMATODE ANCYLOSTOMA CANINUM
Overview
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.
About this Structure
1COU is a Single protein structure of sequence from Ancylostoma caninum. Full crystallographic information is available from OCA.
Reference
Inherent flexibility in a potent inhibitor of blood coagulation, recombinant nematode anticoagulant protein c2., Duggan BM, Dyson HJ, Wright PE, Eur J Biochem. 1999 Oct;265(2):539-48. PMID:10504384
Page seeded by OCA on Sun Nov 25 01:45:48 2007
