1zhp
From Proteopedia
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| - | [[Image:1zhp.gif|left|200px]] | + | [[Image:1zhp.gif|left|200px]] |
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| - | '''Crystal Structure of the Catalytic Domain of Coagulation Factor XI in Complex with Benzamidine (S434A-T475A-K505 Mutant)''' | + | {{Structure |
| + | |PDB= 1zhp |SIZE=350|CAPTION= <scene name='initialview01'>1zhp</scene>, resolution 2.70Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=BEN:BENZAMIDINE'>BEN</scene> and <scene name='pdbligand=GSH:GLUTATHIONE'>GSH</scene> | ||
| + | |ACTIVITY= [http://en.wikipedia.org/wiki/Coagulation_factor_XIa Coagulation factor XIa], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.27 3.4.21.27] | ||
| + | |GENE= F11 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | }} | ||
| + | |||
| + | '''Crystal Structure of the Catalytic Domain of Coagulation Factor XI in Complex with Benzamidine (S434A-T475A-K505 Mutant)''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1ZHP is a [ | + | 1ZHP is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ZHP OCA]. |
==Reference== | ==Reference== | ||
| - | Mutation of surface residues to promote crystallization of activated factor XI as a complex with benzamidine: an essential step for the iterative structure-based design of factor XI inhibitors., Jin L, Pandey P, Babine RE, Weaver DT, Abdel-Meguid SS, Strickler JE, Acta Crystallogr D Biol Crystallogr. 2005 Oct;61(Pt 10):1418-25. Epub 2005, Sep 28. PMID:[http:// | + | Mutation of surface residues to promote crystallization of activated factor XI as a complex with benzamidine: an essential step for the iterative structure-based design of factor XI inhibitors., Jin L, Pandey P, Babine RE, Weaver DT, Abdel-Meguid SS, Strickler JE, Acta Crystallogr D Biol Crystallogr. 2005 Oct;61(Pt 10):1418-25. Epub 2005, Sep 28. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16204896 16204896] |
[[Category: Coagulation factor XIa]] | [[Category: Coagulation factor XIa]] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
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[[Category: factor xi; benzamidine]] | [[Category: factor xi; benzamidine]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 15:35:36 2008'' |
Revision as of 13:35, 20 March 2008
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| , resolution 2.70Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | and | ||||||
| Gene: | F11 (Homo sapiens) | ||||||
| Activity: | Coagulation factor XIa, with EC number 3.4.21.27 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal Structure of the Catalytic Domain of Coagulation Factor XI in Complex with Benzamidine (S434A-T475A-K505 Mutant)
Contents |
Overview
Activated factor XI (FXIa) is a key enzyme in the amplification phase of the blood-coagulation cascade. Thus, a selective FXIa inhibitor may have lesser bleeding liabilities and provide a safe alternative for antithrombosis therapy to available drugs on the market. In a previous report, the crystal structures of the catalytic domain of FXIa (rhFXI(370-607)) in complex with various ecotin mutants have been described. However, ecotin forms a matrix-like interaction with rhFXI(370-607) and is impossible to displace with small-molecule inhibitors; ecotin crystals are therefore not suitable for iterative structure-based ligand design. In addition, rhFXI(370-607) did not crystallize in the presence of small-molecule ligands. In order to obtain the crystal structure of rhFXI(370-607) with a weak small-molecule ligand, namely benzamidine, several rounds of surface-residue mutation were implemented to promote crystal formation of rhFXI(370-607). A quadruple mutant of rhFXI(370-607) (rhFXI(370-607)-S434A,T475A,C482S,K437A) readily crystallized in the presence of benzamidine. The benzamidine in the preformed crystals was easily exchanged with other FXIa small-molecule inhibitors. These crystals have facilitated the structure-based design of small-molecule FXIa inhibitors.
Disease
Known diseases associated with this structure: Factor XI deficiency, autosomal dominant OMIM:[264900], Factor XI deficiency, autosomal recessive OMIM:[264900]
About this Structure
1ZHP is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Mutation of surface residues to promote crystallization of activated factor XI as a complex with benzamidine: an essential step for the iterative structure-based design of factor XI inhibitors., Jin L, Pandey P, Babine RE, Weaver DT, Abdel-Meguid SS, Strickler JE, Acta Crystallogr D Biol Crystallogr. 2005 Oct;61(Pt 10):1418-25. Epub 2005, Sep 28. PMID:16204896
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