2c8w: Difference between revisions
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|PDB= 2c8w |SIZE=350|CAPTION= <scene name='initialview01'>2c8w</scene>, resolution 1.96Å | |PDB= 2c8w |SIZE=350|CAPTION= <scene name='initialview01'>2c8w</scene>, resolution 1.96Å | ||
|SITE= <scene name='pdbsite=AC1:C7m+Binding+Site+For+Chain+B'>AC1</scene> | |SITE= <scene name='pdbsite=AC1:C7m+Binding+Site+For+Chain+B'>AC1</scene> | ||
|LIGAND= | |LIGAND= <scene name='pdbligand=C7M:(2S,3R)-N-[5-CHLORO-2-(2,3-DIHYDRO-1H-TETRAZOL-1-YL)BENZYL]-3-HYDROXY-4-{[(4-METHOXYPHENYL)SULFONYL]AMINO}-1-PHENYLBUTAN-2-AMINIUM'>C7M</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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= | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2c8w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2c8w OCA], [http://www.ebi.ac.uk/pdbsum/2c8w PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2c8w RCSB]</span> | |||
}} | }} | ||
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==Overview== | ==Overview== | ||
The screening of fragments is an alternative approach to high-throughput screening for the identification of leads for therapeutic targets. Fragment hits have been discovered using X-ray crystallographic screening of protein crystals of the serine protease enzyme thrombin. The fragment library was designed to avoid any well-precedented, strongly basic functionality. Screening hits included a novel ligand (3), which binds exclusively to the S2-S4 pocket, in addition to smaller fragments which bind to the S1 pocket. The structure of these protein-ligand complexes are presented. A chemistry strategy to link two such fragments together and to synthesize larger drug-sized compounds resulted in the efficient identification of hybrid inhibitors with nanomolar potency (e.g., 7, IC50 = 3.7 nM). These potent ligands occupy the same area of the active site as previously described peptidic inhibitors, while having very different chemical architecture. | The screening of fragments is an alternative approach to high-throughput screening for the identification of leads for therapeutic targets. Fragment hits have been discovered using X-ray crystallographic screening of protein crystals of the serine protease enzyme thrombin. The fragment library was designed to avoid any well-precedented, strongly basic functionality. Screening hits included a novel ligand (3), which binds exclusively to the S2-S4 pocket, in addition to smaller fragments which bind to the S1 pocket. The structure of these protein-ligand complexes are presented. A chemistry strategy to link two such fragments together and to synthesize larger drug-sized compounds resulted in the efficient identification of hybrid inhibitors with nanomolar potency (e.g., 7, IC50 = 3.7 nM). These potent ligands occupy the same area of the active site as previously described peptidic inhibitors, while having very different chemical architecture. | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Murray, C W.]] | [[Category: Murray, C W.]] | ||
[[Category: Seavers, L C.A.]] | [[Category: Seavers, L C.A.]] | ||
[[Category: acute phase]] | [[Category: acute phase]] | ||
[[Category: blood coagulation]] | [[Category: blood coagulation]] | ||
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[[Category: zymogen]] | [[Category: zymogen]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 02:18:04 2008'' | ||
