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| - | [[Image:1skz.gif|left|200px]] | + | {{Seed}} |
| | + | [[Image:1skz.png|left|200px]] |
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| | {{STRUCTURE_1skz| PDB=1skz | SCENE= }} | | {{STRUCTURE_1skz| PDB=1skz | SCENE= }} |
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| - | '''PROTEASE INHIBITOR'''
| + | ===PROTEASE INHIBITOR=== |
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| - | ==Overview==
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| - | The three-dimensional structure of antistasin, a potent inhibitor of blood coagulation factor Xa, from the Mexican leech Haementeria officinalis was determined at 1.9 A resolution by X-ray crystallography. The structure reveals a novel protein fold composed of two homologous domains, each resembling the structure of hirustasin, a related 55-residue protease inhibitor. However, hirustasin has a different overall shape than the individual antistasin domains, it contains four rather than two beta-strands, and does not inhibit factor Xa. The two antistasin domains can be subdivided into two similarly sized subdomains with different relative orientations. Consequently, the domain shapes are different, the N-terminal domain being wedge-shaped and the C-terminal domain flat. Docking studies suggest that differences in domain shape enable the N-terminal, but not C-terminal, domain of antistasin to bind and inhibit factor Xa, even though both have a very similar reactive site. Furthermore, a putative exosite binding region could be defined in the N-terminal domain of antistasin, comprising residues 15-17, which is likely to interact with a cluster of positively charged residues on the factor Xa surface (Arg222/Lys223/Lys224). This exosite binding region explains the specificity and inhibitory potency of antistasin towards factor Xa. In the C-terminal domain of antistasin, these exosite interactions are prevented due to the different overall shape of this domain.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_9311976}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 9311976 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_9311976}} |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: Serine protease inhibitor]] | | [[Category: Serine protease inhibitor]] |
| | [[Category: Thrombosis]] | | [[Category: Thrombosis]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 08:49:59 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 12:40:18 2008'' |
Revision as of 09:40, 27 July 2008
Template:STRUCTURE 1skz
PROTEASE INHIBITOR
Template:ABSTRACT PUBMED 9311976
About this Structure
1SKZ is a Single protein structure of sequence from Haementeria officinalis. Full crystallographic information is available from OCA.
Reference
X-ray structure of antistasin at 1.9 A resolution and its modelled complex with blood coagulation factor Xa., Lapatto R, Krengel U, Schreuder HA, Arkema A, de Boer B, Kalk KH, Hol WG, Grootenhuis PD, Mulders JW, Dijkema R, Theunissen HJ, Dijkstra BW, EMBO J. 1997 Sep 1;16(17):5151-61. PMID:9311976
Page seeded by OCA on Sun Jul 27 12:40:18 2008
