1kli: Difference between revisions
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[[Image:1kli.jpg|left|200px]] | [[Image:1kli.jpg|left|200px]] | ||
'''Cofactor-and substrate-assisted activation of factor VIIa''' | {{Structure | ||
|PDB= 1kli |SIZE=350|CAPTION= <scene name='initialview01'>1kli</scene>, resolution 1.69Å | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=BEN:BENZAMIDINE'>BEN</scene> and <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene> | |||
|ACTIVITY= [http://en.wikipedia.org/wiki/Coagulation_factor_VIIa Coagulation factor VIIa], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.21 3.4.21.21] | |||
|GENE= | |||
}} | |||
'''Cofactor-and substrate-assisted activation of factor VIIa''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
1KLI is a [ | 1KLI 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=1KLI OCA]. | ||
==Reference== | ==Reference== | ||
Crystal structures of uninhibited factor VIIa link its cofactor and substrate-assisted activation to specific interactions., Sichler K, Banner DW, D'Arcy A, Hopfner KP, Huber R, Bode W, Kresse GB, Kopetzki E, Brandstetter H, J Mol Biol. 2002 Sep 20;322(3):591-603. PMID:[http:// | Crystal structures of uninhibited factor VIIa link its cofactor and substrate-assisted activation to specific interactions., Sichler K, Banner DW, D'Arcy A, Hopfner KP, Huber R, Bode W, Kresse GB, Kopetzki E, Brandstetter H, J Mol Biol. 2002 Sep 20;322(3):591-603. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/12225752 12225752] | ||
[[Category: Coagulation factor VIIa]] | [[Category: Coagulation factor VIIa]] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
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[[Category: substrate-assisted catalysis]] | [[Category: substrate-assisted catalysis]] | ||
''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 12:19:00 2008'' | ||
Revision as of 13:19, 20 March 2008
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| , resolution 1.69Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , and | ||||||
| Activity: | Coagulation factor VIIa, with EC number 3.4.21.21 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Cofactor-and substrate-assisted activation of factor VIIa
OverviewOverview
Factor VIIa initiates the extrinsic coagulation cascade; this event requires a delicately balanced regulation that is implemented on different levels, including a sophisticated multi-step activation mechanism of factor VII. Its central role in hemostasis and thrombosis makes factor VIIa a key target of pharmaceutical research. We succeeded, for the first time, in recombinantly producing N-terminally truncated factor VII (rf7) in an Escherichia coli expression system by employing an oxidative, in vitro, folding protocol, which depends critically on the presence of ethylene glycol. Activated recombinant factor VIIa (rf7a) was crystallised in the presence of the reversible S1-site inhibitor benzamidine. Comparison of this 1.69A crystal structure with that of an inhibitor-free and sulphate-free, but isomorphous crystal form identified structural details of factor VIIa stimulation. The stabilisation of Asp189-Ser190 by benzamidine and the capping of the intermediate helix by a sulphate ion appear to be sufficient to mimic the disorder-order transition conferred by the cofactor tissue factor (TF) and the substrate factor X. Factor VIIa shares with the homologous factor IXa, but not factor Xa, a bell-shaped activity modulation dependent on ethylene glycol. The ethylene glycol-binding site of rf7a was identified in the vicinity of the 60 loop. Ethylene glycol binding induces a significant conformational rearrangement of the 60 loop. This region serves as a recognition site of the physiologic substrate, factor X, which is common to both factor VIIa and factor IXa. These results provide a mechanistic framework of substrate-assisted catalysis of both factor VIIa and factor IXa.
DiseaseDisease
Known diseases associated with this structure: Factor VII deficiency OMIM:[227500], Myocardial infarction, decreased susceptibility to OMIM:[227500]
About this StructureAbout this Structure
1KLI is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Crystal structures of uninhibited factor VIIa link its cofactor and substrate-assisted activation to specific interactions., Sichler K, Banner DW, D'Arcy A, Hopfner KP, Huber R, Bode W, Kresse GB, Kopetzki E, Brandstetter H, J Mol Biol. 2002 Sep 20;322(3):591-603. PMID:12225752
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