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1cou

From Proteopedia

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[[Image:1cou.gif|left|200px]]
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{{STRUCTURE_1cou| PDB=1cou | SCENE= }}
{{STRUCTURE_1cou| PDB=1cou | SCENE= }}
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'''ANTICOAGULANT PROTEIN FROM THE NEMATODE ANCYLOSTOMA CANINUM'''
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===ANTICOAGULANT PROTEIN FROM THE NEMATODE ANCYLOSTOMA CANINUM===
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==Overview==
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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.
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(as it appears on PubMed at http://www.pubmed.gov), where 10504384 is the PubMed ID number.
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{{ABSTRACT_PUBMED_10504384}}
==About this Structure==
==About this Structure==
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1COU is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Ancylostoma_caninum Ancylostoma caninum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1COU OCA].
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1COU is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Ancylostoma_caninum Ancylostoma caninum]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1COU OCA].
==Reference==
==Reference==
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[[Category: Anticoagulant]]
[[Category: Anticoagulant]]
[[Category: Protease inhibitor]]
[[Category: Protease inhibitor]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 12:57:34 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jun 30 21:02:10 2008''

Revision as of 18:02, 30 June 2008

Image:1cou.png

Template:STRUCTURE 1cou

ANTICOAGULANT PROTEIN FROM THE NEMATODE ANCYLOSTOMA CANINUM

Template:ABSTRACT PUBMED 10504384

About this Structure

1COU is a Single protein structure of sequence from Ancylostoma caninum. Full experimental 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 Mon Jun 30 21:02:10 2008

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