1z6j

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[[Image:1z6j.gif|left|200px]]<br /><applet load="1z6j" size="350" color="white" frame="true" align="right" spinBox="true"
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[[Image:1z6j.gif|left|200px]]
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caption="1z6j, resolution 2.0&Aring;" />
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'''Crystal Structure of a ternary complex of Factor VIIa/Tissue Factor/Pyrazinone Inhibitor'''<br />
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{{Structure
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|PDB= 1z6j |SIZE=350|CAPTION= <scene name='initialview01'>1z6j</scene>, resolution 2.0&Aring;
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|SITE=
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|LIGAND= <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene> and <scene name='pdbligand=PY3:5-[AMINO(IMINO)METHYL]-2-[({[6-[3-AMINO-5-({[(1R)-1-METHYLPROPYL]AMINO}CARBONYL)PHENYL]-3-(ISOPROPYLAMINO)-2-OXOPYRAZIN-1(2H)-YL]ACETYL}AMINO)METHYL]-N-PYRIDIN-4-YLBENZAMIDE'>PY3</scene>
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|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]
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|GENE= F7 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), F3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
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}}
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'''Crystal Structure of a ternary complex of Factor VIIa/Tissue Factor/Pyrazinone Inhibitor'''
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==Overview==
==Overview==
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==About this Structure==
==About this Structure==
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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].
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1Z6J 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=1Z6J OCA].
==Reference==
==Reference==
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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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15913999 15913999]
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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:[http://www.ncbi.nlm.nih.gov/pubmed/15913999 15913999]
[[Category: Coagulation factor VIIa]]
[[Category: Coagulation factor VIIa]]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: tissue factor]]
[[Category: tissue factor]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:12:33 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 15:31:45 2008''

Revision as of 13:31, 20 March 2008

Image:1z6j.gif


PDB ID 1z6j

Drag the structure with the mouse to rotate
, resolution 2.0Å
Ligands: , and
Gene: F7 (Homo sapiens), F3 (Homo sapiens)
Activity: Coagulation factor VIIa, with EC number 3.4.21.21
Coordinates: save as pdb, mmCIF, xml



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. 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

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