1riw

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[[Image:1riw.gif|left|200px]]<br /><applet load="1riw" size="350" color="white" frame="true" align="right" spinBox="true"
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[[Image:1riw.gif|left|200px]]
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caption="1riw, resolution 2.04&Aring;" />
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'''Thrombin in complex with natural product inhibitor Oscillarin'''<br />
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{{Structure
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|PDB= 1riw |SIZE=350|CAPTION= <scene name='initialview01'>1riw</scene>, resolution 2.04&Aring;
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|SITE=
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|LIGAND= <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene> and <scene name='pdbligand=OSC:(2R,3AS,6R,7AS)-N-(2-{1-[AMINO(IMINO)METHYL]-2,5-DIHYDRO-1H-PYRROL-3-YL}ETHYL)-6-HYDROXY-1-{N-[(2S)-2-HYDROXY-3-PHENYLPROPANOYL]PHENYLALANYL}OCTAHYDRO-1H-INDOLE-2-CARBOXAMIDE'>OSC</scene>
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|ACTIVITY= [http://en.wikipedia.org/wiki/Thrombin Thrombin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.5 3.4.21.5]
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|GENE=
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}}
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'''Thrombin in complex with natural product inhibitor Oscillarin'''
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==Overview==
==Overview==
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==About this Structure==
==About this Structure==
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1RIW 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=NAG:'>NAG</scene>, <scene name='pdbligand=SO4:'>SO4</scene>, <scene name='pdbligand=NA:'>NA</scene> and <scene name='pdbligand=OSC:'>OSC</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Thrombin Thrombin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.5 3.4.21.5] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1RIW OCA].
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1RIW 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=1RIW OCA].
==Reference==
==Reference==
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The N-acyloxyiminium ion aza-Prins route to octahydroindoles: total synthesis and structural confirmation of the antithrombotic marine natural product oscillarin., Hanessian S, Tremblay M, Petersen JF, J Am Chem Soc. 2004 May 19;126(19):6064-71. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15137772 15137772]
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The N-acyloxyiminium ion aza-Prins route to octahydroindoles: total synthesis and structural confirmation of the antithrombotic marine natural product oscillarin., Hanessian S, Tremblay M, Petersen JF, J Am Chem Soc. 2004 May 19;126(19):6064-71. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15137772 15137772]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Protein complex]]
[[Category: Protein complex]]
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[[Category: thrombin]]
[[Category: thrombin]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:51:21 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 13:52:21 2008''

Revision as of 11:52, 20 March 2008

Image:1riw.gif


PDB ID 1riw

Drag the structure with the mouse to rotate
, resolution 2.04Å
Ligands: , , and
Activity: Thrombin, with EC number 3.4.21.5
Coordinates: save as pdb, mmCIF, xml



Thrombin in complex with natural product inhibitor Oscillarin


Contents

Overview

The first enantiocontrolled total synthesis of the marine natural product oscillarin is described. The proposed structure and absolute configuration of oscillarin is thus confirmed, and a previously assigned structure of a subunit was shown to be incorrect. The X-ray structure of an oscillarin-thrombin complex was resolved at 2.0 A resolution, which validated its potent inhibitory activity against the enzyme with an IC(50) = 28 nM. Methodology was developed for the synthesis of enantiopure octahydroindole-2-carboxylic acids with usable functionality at C-6. The method consists of the halocarbocyclization of N-acyloxyiminium ions containing an olefinic tether in the presence of tin tetrachloride or tin tetrabromide. This N-acyloxyiminium ion aza-Prins carbocyclization proved to be general for the construction of octahydroindole and perhydroquinoline 2-carboxylic acids. Mechanistic rationales are based on an antiperiplanar attack of the terminal alkene on the iminium ion, leading to an incipient secondary carbocation which is trapped by halide via an equatorial attack. X-ray crystal structures of products corroborate the expected stereochemistry.

Disease

Known diseases associated with this structure: Dysprothrombinemia OMIM:[176930], Hyperprothrombinemia OMIM:[176930], Hypoprothrombinemia OMIM:[176930]

About this Structure

1RIW is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

Reference

The N-acyloxyiminium ion aza-Prins route to octahydroindoles: total synthesis and structural confirmation of the antithrombotic marine natural product oscillarin., Hanessian S, Tremblay M, Petersen JF, J Am Chem Soc. 2004 May 19;126(19):6064-71. PMID:15137772

Page seeded by OCA on Thu Mar 20 13:52:21 2008

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