1sb1

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[[Image:1sb1.gif|left|200px]]<br /><applet load="1sb1" size="350" color="white" frame="true" align="right" spinBox="true"
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[[Image:1sb1.gif|left|200px]]
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caption="1sb1, resolution 1.90&Aring;" />
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'''Novel Non-Covalent Thrombin Inhibitors Incorporating P1 4,5,6,7-Tetrahydrobenzothiazole Arginine Side Chain Mimetics'''<br />
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{{Structure
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|PDB= 1sb1 |SIZE=350|CAPTION= <scene name='initialview01'>1sb1</scene>, resolution 1.90&Aring;
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|SITE=
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|LIGAND= <scene name='pdbligand=NA:SODIUM+ION'>NA</scene> and <scene name='pdbligand=165:N-(BENZYLSULFONYL)-3-CYCLOHEXYLALANYL-N-(2-AMINO-1,3-BENZOTHIAZOL-6-YL)PROLINAMIDE'>165</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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'''Novel Non-Covalent Thrombin Inhibitors Incorporating P1 4,5,6,7-Tetrahydrobenzothiazole Arginine Side Chain Mimetics'''
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==Overview==
==Overview==
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==About this Structure==
==About this Structure==
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1SB1 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=NA:'>NA</scene> and <scene name='pdbligand=165:'>165</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=1SB1 OCA].
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1SB1 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=1SB1 OCA].
==Reference==
==Reference==
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Novel non-covalent thrombin inhibitors incorporating P(1) 4,5,6,7-tetrahydrobenzothiazole arginine side chain mimetics., Marinko P, Krbavcic A, Mlinsek G, Solmajer T, Bakija AT, Stegnar M, Stojan J, Kikelj D, Eur J Med Chem. 2004 Mar;39(3):257-65. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15051174 15051174]
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Novel non-covalent thrombin inhibitors incorporating P(1) 4,5,6,7-tetrahydrobenzothiazole arginine side chain mimetics., Marinko P, Krbavcic A, Mlinsek G, Solmajer T, Bakija AT, Stegnar M, Stojan J, Kikelj D, Eur J Med Chem. 2004 Mar;39(3):257-65. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15051174 15051174]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Protein complex]]
[[Category: Protein complex]]
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[[Category: thrombin; inhibition; hirugen; serine protease inhibitor]]
[[Category: thrombin; inhibition; hirugen; serine protease inhibitor]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:59:40 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 14:02:40 2008''

Revision as of 12:02, 20 March 2008


PDB ID 1sb1

Drag the structure with the mouse to rotate
, resolution 1.90Å
Ligands: and
Activity: Thrombin, with EC number 3.4.21.5
Coordinates: save as pdb, mmCIF, xml



Novel Non-Covalent Thrombin Inhibitors Incorporating P1 4,5,6,7-Tetrahydrobenzothiazole Arginine Side Chain Mimetics


Contents

Overview

The design, synthesis and biological activity of a series of novel non-covalent D-Phe-Pro-Arg motif-based thrombin inhibitors incorporating 4,5,6,7-tetrahydrobenzothiazol-2-amine as a novel arginine surrogate are described. Compound 9, the most potent in the series of thrombin inhibitors, exhibited an in vitro K(i) of 128 nM and 342-fold selectivity against trypsin. The binding mode of this novel class of thrombin inhibitors in the enzyme active site, based on the X-ray crystal structure of compound 9 co-crystallized with human alpha-thrombin, is discussed.

Disease

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

About this Structure

1SB1 is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Novel non-covalent thrombin inhibitors incorporating P(1) 4,5,6,7-tetrahydrobenzothiazole arginine side chain mimetics., Marinko P, Krbavcic A, Mlinsek G, Solmajer T, Bakija AT, Stegnar M, Stojan J, Kikelj D, Eur J Med Chem. 2004 Mar;39(3):257-65. PMID:15051174

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