1wss
From Proteopedia
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|PDB= 1wss |SIZE=350|CAPTION= <scene name='initialview01'>1wss</scene>, resolution 2.60Å | |PDB= 1wss |SIZE=350|CAPTION= <scene name='initialview01'>1wss</scene>, resolution 2.60Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand= | + | |LIGAND= <scene name='pdbligand=3CB:N-[(3-CARBOXYBENZYL)SULFONYL]ISOLEUCYL-N~1~-{4-[AMINO(IMINO)METHYL]BENZYL}-5-IMINOORNITHINAMIDE'>3CB</scene>, <scene name='pdbligand=BGC:BETA-D-GLUCOSE'>BGC</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CGU:GAMMA-CARBOXY-GLUTAMIC+ACID'>CGU</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</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] | + | |ACTIVITY= <span class='plainlinks'>[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] </span> |
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1wqv|1WQV]], [[1dan|1DAN]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1wss FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1wss OCA], [http://www.ebi.ac.uk/pdbsum/1wss PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1wss RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==Overview== | ||
The crystal structure of human factor VIIa/soluble tissue factor (FVIIa/sTF) in complex with a highly selective peptide-mimetic FVIIa inhibitor which shows 1670-fold selectivity against thrombin inhibition has been solved at 2.6 A resolution. The inhibitor is bound to FVIIa/sTF at the S1, S2 and S3 sites and at the additional S1 subsite. Two charged groups, the amidino group in P2 and the carboxylate group in P4, form ionic interactions with Asp60 and Lys192 of FVIIa, respectively. Structural comparisons between factor VIIa and thrombin show that thrombin has oppositely charged residues, Lys60F and Glu192, in the S2 site and the S1 subsites, respectively. These data suggest that the utilization of the differences of charge distribution in the S2 site and the S1 subsites between FVIIa and thrombin is critical for achieving high selectivity against thrombin inhibition. These results will provide valuable information for the structure-based drug design of specific inhibitors for FVIIa/TF. | The crystal structure of human factor VIIa/soluble tissue factor (FVIIa/sTF) in complex with a highly selective peptide-mimetic FVIIa inhibitor which shows 1670-fold selectivity against thrombin inhibition has been solved at 2.6 A resolution. The inhibitor is bound to FVIIa/sTF at the S1, S2 and S3 sites and at the additional S1 subsite. Two charged groups, the amidino group in P2 and the carboxylate group in P4, form ionic interactions with Asp60 and Lys192 of FVIIa, respectively. Structural comparisons between factor VIIa and thrombin show that thrombin has oppositely charged residues, Lys60F and Glu192, in the S2 site and the S1 subsites, respectively. These data suggest that the utilization of the differences of charge distribution in the S2 site and the S1 subsites between FVIIa and thrombin is critical for achieving high selectivity against thrombin inhibition. These results will provide valuable information for the structure-based drug design of specific inhibitors for FVIIa/TF. | ||
| - | |||
| - | ==Disease== | ||
| - | Known diseases associated with this structure: Esophageal squamous cell carcinoma OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=606551 606551]], Factor VII deficiency OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=227500 227500]], Myocardial infarction, decreased susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=227500 227500]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Watanabe, Y.]] | [[Category: Watanabe, Y.]] | ||
[[Category: Yabuta, N.]] | [[Category: Yabuta, N.]] | ||
| - | [[Category: 3CB]] | ||
| - | [[Category: BGC]] | ||
| - | [[Category: CA]] | ||
| - | [[Category: FUC]] | ||
[[Category: serine protease]] | [[Category: serine protease]] | ||
| - | ''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 00:40:29 2008'' |
Revision as of 21:40, 30 March 2008
| |||||||
| , resolution 2.60Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , , , | ||||||
| Activity: | Coagulation factor VIIa, with EC number 3.4.21.21 | ||||||
| Related: | 1WQV, 1DAN
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Human Factor Viia-Tissue Factor in Complex with peprid mimetic inhibitor that has two charge groups in P2 and P4
Overview
The crystal structure of human factor VIIa/soluble tissue factor (FVIIa/sTF) in complex with a highly selective peptide-mimetic FVIIa inhibitor which shows 1670-fold selectivity against thrombin inhibition has been solved at 2.6 A resolution. The inhibitor is bound to FVIIa/sTF at the S1, S2 and S3 sites and at the additional S1 subsite. Two charged groups, the amidino group in P2 and the carboxylate group in P4, form ionic interactions with Asp60 and Lys192 of FVIIa, respectively. Structural comparisons between factor VIIa and thrombin show that thrombin has oppositely charged residues, Lys60F and Glu192, in the S2 site and the S1 subsites, respectively. These data suggest that the utilization of the differences of charge distribution in the S2 site and the S1 subsites between FVIIa and thrombin is critical for achieving high selectivity against thrombin inhibition. These results will provide valuable information for the structure-based drug design of specific inhibitors for FVIIa/TF.
About this Structure
1WSS is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structure of human factor VIIa/tissue factor in complex with a peptide-mimetic inhibitor: high selectivity against thrombin by introducing two charged groups in P2 and P4., Kadono S, Sakamoto A, Kikuchi Y, Oh-Eda M, Yabuta N, Koga T, Hattori K, Shiraishi T, Haramura M, Kodama H, Ono Y, Esaki T, Sato H, Watanabe Y, Itoh S, Ohta M, Kozono T, Acta Crystallogr Sect F Struct Biol Cryst Commun. 2005 Feb 1;61(Pt, 2):169-73. Epub 2005 Jan 20. PMID:16510984
Page seeded by OCA on Mon Mar 31 00:40:29 2008
Categories: Coagulation factor VIIa | Homo sapiens | Protein complex | Esaki, T. | Haramura, M. | Hattori, K. | Itoh, S. | Kadono, S. | Kikuchi, Y. | Kodama, H. | Koga, T. | Kozono, T. | Oh-Eda, M. | Ohta, M. | Ono, Y. | Sakamoto, A. | Sato, H. | Shiraishi, T. | Watanabe, Y. | Yabuta, N. | Serine protease
