1way
From Proteopedia
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|PDB= 1way |SIZE=350|CAPTION= <scene name='initialview01'>1way</scene>, resolution 2.02Å | |PDB= 1way |SIZE=350|CAPTION= <scene name='initialview01'>1way</scene>, resolution 2.02Å | ||
|SITE= <scene name='pdbsite=AC1:Dms+Binding+Site+For+Chain+B'>AC1</scene> | |SITE= <scene name='pdbsite=AC1:Dms+Binding+Site+For+Chain+B'>AC1</scene> | ||
| - | |LIGAND= <scene name='pdbligand=L02:4-[3-(4-CHLOROPHENYL)-1H-PYRAZOL-5-YL]PIPERIDINE'>L02</scene> | + | |LIGAND= <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=L02:4-[3-(4-CHLOROPHENYL)-1H-PYRAZOL-5-YL]PIPERIDINE'>L02</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=1way FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1way OCA], [http://www.ebi.ac.uk/pdbsum/1way PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1way RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==Overview== | ||
Fragment screening offers an alternative to traditional screening for discovering new leads in drug discovery programs. This paper describes a fragment screening methodology based on high throughput X-ray crystallography. The method is illustrated against five proteins (p38 MAP kinase, CDK2, thrombin, ribonuclease A, and PTP1B). The fragments identified have weak potency (>100 microM) but are efficient binders relative to their size and may therefore represent suitable starting points for evolution to good quality lead compounds. The examples illustrate that a range of molecular interactions (i.e., lipophilic, charge-charge, neutral hydrogen bonds) can drive fragment binding and also that fragments can induce protein movement. We believe that the method has great potential for the discovery of novel lead compounds against a range of targets, and the companion paper illustrates how lead compounds have been identified for p38 MAP kinase starting from fragments such as those described in this paper. | Fragment screening offers an alternative to traditional screening for discovering new leads in drug discovery programs. This paper describes a fragment screening methodology based on high throughput X-ray crystallography. The method is illustrated against five proteins (p38 MAP kinase, CDK2, thrombin, ribonuclease A, and PTP1B). The fragments identified have weak potency (>100 microM) but are efficient binders relative to their size and may therefore represent suitable starting points for evolution to good quality lead compounds. The examples illustrate that a range of molecular interactions (i.e., lipophilic, charge-charge, neutral hydrogen bonds) can drive fragment binding and also that fragments can induce protein movement. We believe that the method has great potential for the discovery of novel lead compounds against a range of targets, and the companion paper illustrates how lead compounds have been identified for p38 MAP kinase starting from fragments such as those described in this paper. | ||
| - | |||
| - | ==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: Murray, C W.]] | [[Category: Murray, C W.]] | ||
[[Category: Tickle, I J.]] | [[Category: Tickle, I J.]] | ||
| - | [[Category: DMS]] | ||
| - | [[Category: L02]] | ||
[[Category: acute phase]] | [[Category: acute phase]] | ||
[[Category: blood coagulation]] | [[Category: blood coagulation]] | ||
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[[Category: vitamin k]] | [[Category: vitamin k]] | ||
| - | ''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 00:33:42 2008'' |
Revision as of 21:33, 30 March 2008
| |||||||
| , resolution 2.02Å | |||||||
|---|---|---|---|---|---|---|---|
| Sites: | |||||||
| Ligands: | , , | ||||||
| Activity: | Thrombin, with EC number 3.4.21.5 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
ACTIVE SITE THROMBIN INHIBITORS
Overview
Fragment screening offers an alternative to traditional screening for discovering new leads in drug discovery programs. This paper describes a fragment screening methodology based on high throughput X-ray crystallography. The method is illustrated against five proteins (p38 MAP kinase, CDK2, thrombin, ribonuclease A, and PTP1B). The fragments identified have weak potency (>100 microM) but are efficient binders relative to their size and may therefore represent suitable starting points for evolution to good quality lead compounds. The examples illustrate that a range of molecular interactions (i.e., lipophilic, charge-charge, neutral hydrogen bonds) can drive fragment binding and also that fragments can induce protein movement. We believe that the method has great potential for the discovery of novel lead compounds against a range of targets, and the companion paper illustrates how lead compounds have been identified for p38 MAP kinase starting from fragments such as those described in this paper.
About this Structure
1WAY is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Fragment-based lead discovery using X-ray crystallography., Hartshorn MJ, Murray CW, Cleasby A, Frederickson M, Tickle IJ, Jhoti H, J Med Chem. 2005 Jan 27;48(2):403-13. PMID:15658854
Page seeded by OCA on Mon Mar 31 00:33:42 2008
Categories: Homo sapiens | Protein complex | Thrombin | Cleasby, A. | Frederickson, M. | Hartshorn, M J. | Jhoti, H. | Murray, C W. | Tickle, I J. | Acute phase | Blood coagulation | Calcium-binding | Direct protein sequencing | Disease mutation | Gamma-carboxyglutamic acid | Glycoprotein | Hydrolase | Kringle | Plasma | Polymorphism | Protease | Serine protease | Vitamin k
