1sl3

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[[Image:1sl3.jpg|left|200px]]<br /><applet load="1sl3" size="350" color="white" frame="true" align="right" spinBox="true"
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[[Image:1sl3.jpg|left|200px]]
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caption="1sl3, resolution 1.81&Aring;" />
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'''crystal structue of Thrombin in complex with a potent P1 heterocycle-Aryl based inhibitor'''<br />
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{{Structure
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|PDB= 1sl3 |SIZE=350|CAPTION= <scene name='initialview01'>1sl3</scene>, resolution 1.81&Aring;
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|SITE=
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|LIGAND= <scene name='pdbligand=170:(2-[6-CHLORO-3-{[2,2-DIFLUORO-2-(1-OXIDOPYRIDIN-2-YL)ETHYL]AMINO}-2-OXOPYRAZIN-1(2H)-YL]-N-[5-CHLORO-2-(1H-TETRAZOL-1-YL)BENZYL]ACETAMIDE'>170</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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'''crystal structue of Thrombin in complex with a potent P1 heterocycle-Aryl based inhibitor'''
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==Overview==
==Overview==
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==About this Structure==
==About this Structure==
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1SL3 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=170:'>170</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. 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=1SL3 OCA].
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1SL3 is a [[Single protein]] structure of sequence 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=1SL3 OCA].
==Reference==
==Reference==
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Discovery and evaluation of potent P1 aryl heterocycle-based thrombin inhibitors., Young MB, Barrow JC, Glass KL, Lundell GF, Newton CL, Pellicore JM, Rittle KE, Selnick HG, Stauffer KJ, Vacca JP, Williams PD, Bohn D, Clayton FC, Cook JJ, Krueger JA, Kuo LC, Lewis SD, Lucas BJ, McMasters DR, Miller-Stein C, Pietrak BL, Wallace AA, White RB, Wong B, Yan Y, Nantermet PG, J Med Chem. 2004 Jun 3;47(12):2995-3008. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15163182 15163182]
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Discovery and evaluation of potent P1 aryl heterocycle-based thrombin inhibitors., Young MB, Barrow JC, Glass KL, Lundell GF, Newton CL, Pellicore JM, Rittle KE, Selnick HG, Stauffer KJ, Vacca JP, Williams PD, Bohn D, Clayton FC, Cook JJ, Krueger JA, Kuo LC, Lewis SD, Lucas BJ, McMasters DR, Miller-Stein C, Pietrak BL, Wallace AA, White RB, Wong B, Yan Y, Nantermet PG, J Med Chem. 2004 Jun 3;47(12):2995-3008. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15163182 15163182]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Single protein]]
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[[Category: thrombin inhibitor complex]]
[[Category: thrombin inhibitor complex]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:02:39 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 14:06:20 2008''

Revision as of 12:06, 20 March 2008

Image:1sl3.jpg


PDB ID 1sl3

Drag the structure with the mouse to rotate
, resolution 1.81Å
Ligands:
Activity: Thrombin, with EC number 3.4.21.5
Coordinates: save as pdb, mmCIF, xml



crystal structue of Thrombin in complex with a potent P1 heterocycle-Aryl based inhibitor


Contents

Overview

In an effort to discover potent, clinically useful thrombin inhibitors, a rapid analogue synthetic approach was used to explore the P(1) region. Various benzylamines were coupled to a pyridine/pyrazinone P(2)-P(3) template. One compound with an o-thiadiazole benzylic substitution was found to have a thrombin K(i) of 0.84 nM. A study of ortho-substituted five-membered-ring heterocycles was undertaken and subsequently demonstrated that the o-triazole and tetrazole rings were optimal. Combination of these potent P(1) aryl heterocycles with a variety of P(2)-P(3) groups produced a compound with an extraordinary thrombin inhibitory activity of 1.4 pM. It is hoped that this potency enhancement in P(1) will allow for more diversification in the P(2)-P(3) region to ultimately address additional pharmacological concerns.

Disease

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

About this Structure

1SL3 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Discovery and evaluation of potent P1 aryl heterocycle-based thrombin inhibitors., Young MB, Barrow JC, Glass KL, Lundell GF, Newton CL, Pellicore JM, Rittle KE, Selnick HG, Stauffer KJ, Vacca JP, Williams PD, Bohn D, Clayton FC, Cook JJ, Krueger JA, Kuo LC, Lewis SD, Lucas BJ, McMasters DR, Miller-Stein C, Pietrak BL, Wallace AA, White RB, Wong B, Yan Y, Nantermet PG, J Med Chem. 2004 Jun 3;47(12):2995-3008. PMID:15163182

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