1zhr
From Proteopedia
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|SITE= | |SITE= | ||
|LIGAND= <scene name='pdbligand=BEN:BENZAMIDINE'>BEN</scene> | |LIGAND= <scene name='pdbligand=BEN:BENZAMIDINE'>BEN</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] | + | |ACTIVITY= <span class='plainlinks'>[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] </span> |
|GENE= F11 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= F11 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1zhm|1ZHM]], [[1zhp|1ZHP]], [[1zjd|1ZJD]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1zhr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1zhr OCA], [http://www.ebi.ac.uk/pdbsum/1zhr PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1zhr RCSB]</span> | ||
}} | }} | ||
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==Disease== | ==Disease== | ||
| - | Known | + | Known disease associated with this structure: Factor XI deficiency, autosomal dominant OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=264900 264900]], Factor XI deficiency, autosomal recessive OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=264900 264900]] |
==About this Structure== | ==About this Structure== | ||
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[[Category: Strickler, J E.]] | [[Category: Strickler, J E.]] | ||
[[Category: Weaver, D T.]] | [[Category: Weaver, D T.]] | ||
| - | [[Category: | + | [[Category: benzamidine]] |
| - | [[Category: factor xi | + | [[Category: factor xi]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 01:36:53 2008'' |
Revision as of 22:36, 30 March 2008
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| , resolution 1.73Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Gene: | F11 (Homo sapiens) | ||||||
| Activity: | Coagulation factor XIa, with EC number 3.4.21.27 | ||||||
| Related: | 1ZHM, 1ZHP, 1ZJD
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal Structure of the Catalytic Domain of Coagulation Factor XI in Complex with Benzamidine (S434A-T475A-C482S-K437A 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 disease associated with this structure: Factor XI deficiency, autosomal dominant OMIM:[264900], Factor XI deficiency, autosomal recessive OMIM:[264900]
About this Structure
1ZHR 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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