1wtg
From Proteopedia
(New page: 200px<br /> <applet load="1wtg" size="450" color="white" frame="true" align="right" spinBox="true" caption="1wtg, resolution 2.20Å" /> '''Human Factor Viia-T...) |
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| - | [[Image:1wtg.gif|left|200px]]<br /> | + | [[Image:1wtg.gif|left|200px]]<br /><applet load="1wtg" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1wtg" size=" | + | |
caption="1wtg, resolution 2.20Å" /> | caption="1wtg, resolution 2.20Å" /> | ||
'''Human Factor Viia-Tissue Factor Complexed with ethylsulfonamide-D-biphenylalanine-Gln-p-aminobenzamidine'''<br /> | '''Human Factor Viia-Tissue Factor Complexed with ethylsulfonamide-D-biphenylalanine-Gln-p-aminobenzamidine'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Selective factor VIIa-tissue factor complex (FVIIa/TF) inhibition is seen | + | Selective factor VIIa-tissue factor complex (FVIIa/TF) inhibition is seen as a promising target for developing new anticoagulant drugs. A novel peptide mimetic factor VIIa inhibitor, ethylsulfonamide-d-biphenylalanine-Gln-p-aminobenzamidine, shows 100-fold selectivity against thrombin in spite of its large P3 moiety, unlike previously reported FVIIa/TF selective inhibitors. X-ray crystal structure analysis reveals that the large P3 moiety, d-biphenylalanine, and the small P4 moiety, ethylsulfonamide, make novel interactions with the 170-loop and Lys192 of FVIIa/TF, respectively, accompanying ligand-induced conformational changes of the 170-loop, Gln217, and Lys192. Structural comparisons of FVIIa with thrombin and amino acid sequence comparisons among coagulation serine proteases suggest that these interactions play an important role in achieving selective inhibition for FVIIa/TF. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1WTG is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with BGC, FUC, CA and 3BP as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http:// | + | 1WTG is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=BGC:'>BGC</scene>, <scene name='pdbligand=FUC:'>FUC</scene>, <scene name='pdbligand=CA:'>CA</scene> and <scene name='pdbligand=3BP:'>3BP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1WTG OCA]. |
==Reference== | ==Reference== | ||
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[[Category: serine protease]] | [[Category: serine protease]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:47:55 2008'' |
Revision as of 13:48, 21 February 2008
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Human Factor Viia-Tissue Factor Complexed with ethylsulfonamide-D-biphenylalanine-Gln-p-aminobenzamidine
Contents |
Overview
Selective factor VIIa-tissue factor complex (FVIIa/TF) inhibition is seen as a promising target for developing new anticoagulant drugs. A novel peptide mimetic factor VIIa inhibitor, ethylsulfonamide-d-biphenylalanine-Gln-p-aminobenzamidine, shows 100-fold selectivity against thrombin in spite of its large P3 moiety, unlike previously reported FVIIa/TF selective inhibitors. X-ray crystal structure analysis reveals that the large P3 moiety, d-biphenylalanine, and the small P4 moiety, ethylsulfonamide, make novel interactions with the 170-loop and Lys192 of FVIIa/TF, respectively, accompanying ligand-induced conformational changes of the 170-loop, Gln217, and Lys192. Structural comparisons of FVIIa with thrombin and amino acid sequence comparisons among coagulation serine proteases suggest that these interactions play an important role in achieving selective inhibition for FVIIa/TF.
Disease
Known diseases associated with this structure: Esophageal squamous cell carcinoma OMIM:[606551], Factor VII deficiency OMIM:[227500], Myocardial infarction, decreased susceptibility to OMIM:[227500]
About this Structure
1WTG is a Protein complex structure of sequences from Homo sapiens with , , and as ligands. Active as Coagulation factor VIIa, with EC number 3.4.21.21 Full crystallographic information is available from OCA.
Reference
Novel interactions of large P3 moiety and small P4 moiety in the binding of the peptide mimetic factor VIIa inhibitor., Kadono S, Sakamoto A, Kikuchi Y, Oh-Eda M, Yabuta N, Yoshihashi K, Kitazawa T, Suzuki T, Koga T, Hattori K, Shiraishi T, Haramura M, Kodama H, Ono Y, Esaki T, Sato H, Watanabe Y, Itoh S, Ohta M, Kozono T, Biochem Biophys Res Commun. 2005 Jan 28;326(4):859-65. PMID:15607748
Page seeded by OCA on Thu Feb 21 15:47:55 2008
Categories: Coagulation factor VIIa | Homo sapiens | Protein complex | Esaki, T. | Haramura, H. | Hattori, K. | Itoh, S. | Kadono, S. | Kikuchi, Y. | Kitazawa, K. | Kodama, M. | Koga, T. | Kozono, T. | Oh-Eda, M. | Ohta, M. | Ono, Y. | Sakamoto, S. | Sato, H. | Shiraishi, T. | Suzuki, T. | Watanabe, Y. | Yabuta, N. | Yoshihashi, T. | 3BP | BGC | CA | FUC | Serine protease
