1fjs
From Proteopedia
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| - | [[Image:1fjs.jpg|left|200px]] | + | [[Image:1fjs.jpg|left|200px]] |
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| - | '''CRYSTAL STRUCTURE OF THE INHIBITOR ZK-807834 (CI-1031) COMPLEXED WITH FACTOR XA''' | + | {{Structure |
| + | |PDB= 1fjs |SIZE=350|CAPTION= <scene name='initialview01'>1fjs</scene>, resolution 1.92Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=Z34:N-[2-[5-[AMINO(IMINO)METHYL]-2-HYDROXYPHENOXY]-3,5-DIFLUORO-6-[3-(4,5-DIHYDRO-1-METHYL-1H-IMIDAZOL-2-YL)PHENOXY]PYRIDIN-4-YL]-N-METHYLGLYCINE'>Z34</scene> and <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene> | ||
| + | |ACTIVITY= [http://en.wikipedia.org/wiki/Coagulation_factor_Xa Coagulation factor Xa], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.6 3.4.21.6] | ||
| + | |GENE= | ||
| + | }} | ||
| + | |||
| + | '''CRYSTAL STRUCTURE OF THE INHIBITOR ZK-807834 (CI-1031) COMPLEXED WITH FACTOR XA''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1FJS is a [ | + | 1FJS is a [[Protein complex]] structure of sequences 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=1FJS OCA]. |
==Reference== | ==Reference== | ||
| - | Preparation, characterization, and the crystal structure of the inhibitor ZK-807834 (CI-1031) complexed with factor Xa., Adler M, Davey DD, Phillips GB, Kim SH, Jancarik J, Rumennik G, Light DR, Whitlow M, Biochemistry. 2000 Oct 17;39(41):12534-42. PMID:[http:// | + | Preparation, characterization, and the crystal structure of the inhibitor ZK-807834 (CI-1031) complexed with factor Xa., Adler M, Davey DD, Phillips GB, Kim SH, Jancarik J, Rumennik G, Light DR, Whitlow M, Biochemistry. 2000 Oct 17;39(41):12534-42. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/11027132 11027132] |
[[Category: Coagulation factor Xa]] | [[Category: Coagulation factor Xa]] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
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[[Category: protein inhibitor complex]] | [[Category: protein inhibitor complex]] | ||
| - | ''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 11:10:02 2008'' |
Revision as of 09:10, 20 March 2008
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| , resolution 1.92Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , and | ||||||
| Activity: | Coagulation factor Xa, with EC number 3.4.21.6 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
CRYSTAL STRUCTURE OF THE INHIBITOR ZK-807834 (CI-1031) COMPLEXED WITH FACTOR XA
Contents |
Overview
Factor Xa plays a critical role in the formation of blood clots. This serine protease catalyzes the conversion of prothrombin to thrombin, the first joint step that links the intrinsic and extrinsic coagulation pathways. There is considerable interest in the development of factor Xa inhibitors for the intervention in thrombic diseases. This paper presents the structure of the inhibitor ZK-807834, also known as CI-1031, bound to factor Xa and provides the details of the protein purification and crystallization. Results from mass spectrometry indicate that the factor Xa underwent autolysis during crystallization and the first EGF-like domain was cleaved from the protein. The crystal structure of the complex shows that the amidine of ZK-807834 forms a salt bridge with Asp189 in the S1 pocket and the basic imidazoline fits snugly into the S4 site. The central pyridine ring provides a fairly rigid linker between these groups. This rigidity helps minimize entropic losses during binding. In addition, the structure reveals new interactions that were not found in the previous factor Xa/inhibitor complexes. ZK-807834 forms a strong hydrogen bond between an ionized 2-hydroxy group and Ser195 of factor Xa. There is also an aromatic ring-stacking interaction between the inhibitor and Trp215 in the S4 pocket. These interactions contribute to both the potency of this compound (K(I) = 0.11 nM) and the >2500-fold selectivity against homologous serine proteases such as trypsin.
Disease
Known disease associated with this structure: Factor X deficiency OMIM:[227600]
About this Structure
1FJS is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Preparation, characterization, and the crystal structure of the inhibitor ZK-807834 (CI-1031) complexed with factor Xa., Adler M, Davey DD, Phillips GB, Kim SH, Jancarik J, Rumennik G, Light DR, Whitlow M, Biochemistry. 2000 Oct 17;39(41):12534-42. PMID:11027132
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