1z6j
From Proteopedia
(New page: 200px<br /> <applet load="1z6j" size="450" color="white" frame="true" align="right" spinBox="true" caption="1z6j, resolution 2.0Å" /> '''Crystal Structure of...) |
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| - | [[Image:1z6j.gif|left|200px]]<br /> | + | [[Image:1z6j.gif|left|200px]]<br /><applet load="1z6j" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1z6j" size=" | + | |
caption="1z6j, resolution 2.0Å" /> | caption="1z6j, resolution 2.0Å" /> | ||
'''Crystal Structure of a ternary complex of Factor VIIa/Tissue Factor/Pyrazinone Inhibitor'''<br /> | '''Crystal Structure of a ternary complex of Factor VIIa/Tissue Factor/Pyrazinone Inhibitor'''<br /> | ||
==Overview== | ==Overview== | ||
| - | We describe the structure-based design, synthesis, and enzymatic activity | + | We describe the structure-based design, synthesis, and enzymatic activity of a series of substituted pyrazinones as inhibitors of the TF/VIIa complex. These inhibitors contain substituents meta to the P(1) amidine designed to explore additional interactions with the VIIa residues in the so-called 'S(1) side pocket'. A crystal structure of the designed inhibitors demonstrates the ability of the P(1) side pocket moiety to engage Lys192 and main chain of Gly216 via hydrogen bond interactions, thus, providing additional possibility for chemical modification to improve selectivity and/or physical properties of inhibitors. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1Z6J 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 CA, MG and PY3 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:// | + | 1Z6J 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=CA:'>CA</scene>, <scene name='pdbligand=MG:'>MG</scene> and <scene name='pdbligand=PY3:'>PY3</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=1Z6J OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[Category: Kurumbail, R | + | [[Category: Kurumbail, R G.]] |
| - | [[Category: Kusturin, C | + | [[Category: Kusturin, C L.]] |
| - | [[Category: Neumann, W | + | [[Category: Neumann, W L.]] |
| - | [[Category: Poda, G | + | [[Category: Poda, G I.]] |
| - | [[Category: Rahman, H | + | [[Category: Rahman, H K.]] |
| - | [[Category: Sample, K | + | [[Category: Sample, K R.]] |
| - | [[Category: Schweitzer, B | + | [[Category: Schweitzer, B A.]] |
| - | [[Category: Stallings, W | + | [[Category: Stallings, W C.]] |
| - | [[Category: Stegeman, R | + | [[Category: Stegeman, R A.]] |
| - | [[Category: Stevens, A | + | [[Category: Stevens, A M.]] |
[[Category: CA]] | [[Category: CA]] | ||
[[Category: MG]] | [[Category: MG]] | ||
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[[Category: tissue factor]] | [[Category: tissue factor]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:12:33 2008'' |
Revision as of 14:12, 21 February 2008
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Crystal Structure of a ternary complex of Factor VIIa/Tissue Factor/Pyrazinone Inhibitor
Contents |
Overview
We describe the structure-based design, synthesis, and enzymatic activity of a series of substituted pyrazinones as inhibitors of the TF/VIIa complex. These inhibitors contain substituents meta to the P(1) amidine designed to explore additional interactions with the VIIa residues in the so-called 'S(1) side pocket'. A crystal structure of the designed inhibitors demonstrates the ability of the P(1) side pocket moiety to engage Lys192 and main chain of Gly216 via hydrogen bond interactions, thus, providing additional possibility for chemical modification to improve selectivity and/or physical properties of inhibitors.
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
1Z6J 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
Structure-based design and synthesis of pyrazinones containing novel P1 'side pocket' moieties as inhibitors of TF/VIIa., Schweitzer BA, Neumann WL, Rahman HK, Kusturin CL, Sample KR, Poda GI, Kurumbail RG, Stevens AM, Stegeman RA, Stallings WC, South MS, Bioorg Med Chem Lett. 2005 Jun 15;15(12):3006-11. PMID:15913999
Page seeded by OCA on Thu Feb 21 16:12:33 2008
Categories: Coagulation factor VIIa | Homo sapiens | Protein complex | Kurumbail, R G. | Kusturin, C L. | Neumann, W L. | Poda, G I. | Rahman, H K. | Sample, K R. | Schweitzer, B A. | Stallings, W C. | Stegeman, R A. | Stevens, A M. | CA | MG | PY3 | Benzamidine | Blood coagulation | Cofactor | Enzyme inhibitor complex | Gla | Pyrazinone | Serine protease | Thrombosis | Tissue factor
