1nt1
From Proteopedia
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|PDB= 1nt1 |SIZE=350|CAPTION= <scene name='initialview01'>1nt1</scene>, resolution 2.00Å | |PDB= 1nt1 |SIZE=350|CAPTION= <scene name='initialview01'>1nt1</scene>, resolution 2.00Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand=T76:(6R,21AS)-17-CHLORO-6-CYCLOHEXYL-2,3,6,7,10,11,19,20-OCTAHYDRO-1H,5H-PYRROLO[1,2-K][1,4,8,11,14]BENZOXATETRAAZA-CYCLOHEPTADECINE-5,8,12,21(9H,13H,21AH)-TETRONE'>T76</scene> | + | |LIGAND= <scene name='pdbligand=T76:(6R,21AS)-17-CHLORO-6-CYCLOHEXYL-2,3,6,7,10,11,19,20-OCTAHYDRO-1H,5H-PYRROLO[1,2-K][1,4,8,11,14]BENZOXATETRAAZA-CYCLOHEPTADECINE-5,8,12,21(9H,13H,21AH)-TETRONE'>T76</scene>, <scene name='pdbligand=TYS:SULFONATED+TYROSINE'>TYS</scene> |
| - | |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] | + | |ACTIVITY= <span class='plainlinks'>[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] </span> |
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1nm6|1NM6]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1nt1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1nt1 OCA], [http://www.ebi.ac.uk/pdbsum/1nt1 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1nt1 RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==Overview== | ||
A series of potent and selective proline- and pyrazinone-based macrocyclic thrombin inhibitors is described. Detailed SAR studies led to the incorporation of specific functional groups in the tether that enhanced functional activity against thrombin and provided exquisite selectivity against trypsin and tPA. X-ray crystallography and molecular modeling studies revealed the inhibitor-enzyme interactions responsible for this selectivity. | A series of potent and selective proline- and pyrazinone-based macrocyclic thrombin inhibitors is described. Detailed SAR studies led to the incorporation of specific functional groups in the tether that enhanced functional activity against thrombin and provided exquisite selectivity against trypsin and tPA. X-ray crystallography and molecular modeling studies revealed the inhibitor-enzyme interactions responsible for this selectivity. | ||
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| - | ==Disease== | ||
| - | Known diseases associated with this structure: Dysprothrombinemia OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176930 176930]], Hyperprothrombinemia OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176930 176930]], Hypoprothrombinemia OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176930 176930]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Yan, Y.]] | [[Category: Yan, Y.]] | ||
[[Category: Young, M.]] | [[Category: Young, M.]] | ||
| - | [[Category: T76]] | ||
[[Category: thrombin inhibitor complex]] | [[Category: thrombin inhibitor complex]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 22:35:06 2008'' |
Revision as of 19:35, 30 March 2008
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| , resolution 2.00Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , | ||||||
| Activity: | Thrombin, with EC number 3.4.21.5 | ||||||
| Related: | 1NM6
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
thrombin in complex with selective macrocyclic inhibitor
Overview
A series of potent and selective proline- and pyrazinone-based macrocyclic thrombin inhibitors is described. Detailed SAR studies led to the incorporation of specific functional groups in the tether that enhanced functional activity against thrombin and provided exquisite selectivity against trypsin and tPA. X-ray crystallography and molecular modeling studies revealed the inhibitor-enzyme interactions responsible for this selectivity.
About this Structure
1NT1 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Design and synthesis of potent and selective macrocyclic thrombin inhibitors., Nantermet PG, Barrow JC, Newton CL, Pellicore JM, Young M, Lewis SD, Lucas BJ, Krueger JA, McMasters DR, Yan Y, Kuo LC, Vacca JP, Selnick HG, Bioorg Med Chem Lett. 2003 Aug 18;13(16):2781-4. PMID:12873514
Page seeded by OCA on Sun Mar 30 22:35:06 2008
