2h9e

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{{STRUCTURE_2h9e| PDB=2h9e | SCENE= }}
{{STRUCTURE_2h9e| PDB=2h9e | SCENE= }}
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'''Crystal Structure of FXa/selectide/NAPC2 ternary complex'''
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===Crystal Structure of FXa/selectide/NAPC2 ternary complex===
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==Overview==
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NAPc2, an anticoagulant protein from the hematophagous nematode Ancylostoma caninum evaluated in phase-II/IIa clinical trials, inhibits the extrinsic blood coagulation pathway by a two step mechanism, initially interacting with the hitherto uncharacterized factor Xa exosite involved in macromolecular recognition and subsequently inhibiting factor VIIa (K(i)=8.4 pM) of the factor VIIa/tissue factor complex. NAPc2 is highly flexible, becoming partially ordered and undergoing significant structural changes in the C terminus upon binding to the factor Xa exosite. In the crystal structure of the ternary factor Xa/NAPc2/selectide complex, the binding interface consists of an intermolecular antiparallel beta-sheet formed by the segment of the polypeptide chain consisting of residues 74-80 of NAPc2 with the residues 86-93 of factor Xa that is additional maintained by contacts between the short helical segment (residues 67-73) and a turn (residues 26-29) of NAPc2 with the short C-terminal helix of factor Xa (residues 233-243). This exosite is physiologically highly relevant for the recognition and inhibition of factor X/Xa by macromolecular substrates and provides a structural motif for the development of a new class of inhibitors for the treatment of deep vein thrombosis and angioplasty.
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(as it appears on PubMed at http://www.pubmed.gov), where 17173931 is the PubMed ID number.
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{{ABSTRACT_PUBMED_17173931}}
==About this Structure==
==About this Structure==
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[[Category: Napc2]]
[[Category: Napc2]]
[[Category: Selectide]]
[[Category: Selectide]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 06:01:03 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 19:03:32 2008''

Revision as of 16:03, 28 July 2008

Image:2h9e.png

Template:STRUCTURE 2h9e

Crystal Structure of FXa/selectide/NAPC2 ternary complex

Template:ABSTRACT PUBMED 17173931

About this Structure

2H9E is a Protein complex structure of sequences from Ancylostoma caninum and Homo sapiens. Full crystallographic information is available from OCA.

Reference

Intermolecular interactions and characterization of the novel factor Xa exosite involved in macromolecular recognition and inhibition: crystal structure of human Gla-domainless factor Xa complexed with the anticoagulant protein NAPc2 from the hematophagous nematode Ancylostoma caninum., Murakami MT, Rios-Steiner J, Weaver SE, Tulinsky A, Geiger JH, Arni RK, J Mol Biol. 2007 Feb 16;366(2):602-10. Epub 2006 Nov 14. PMID:17173931

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