1wax
From Proteopedia
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|PDB= 1wax |SIZE=350|CAPTION= <scene name='initialview01'>1wax</scene>, resolution 2.20Å | |PDB= 1wax |SIZE=350|CAPTION= <scene name='initialview01'>1wax</scene>, resolution 2.20Å | ||
|SITE= <scene name='pdbsite=AC1:Lo1+Binding+Site+For+Chain+A'>AC1</scene> | |SITE= <scene name='pdbsite=AC1:Lo1+Binding+Site+For+Chain+A'>AC1</scene> | ||
| - | |LIGAND= | + | |LIGAND= <scene name='pdbligand=LO1:[[4-(AMINOMETHYL)PHENYL]AMINO]OXO-ACETIC+ACID,'>LO1</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene> |
| - | |ACTIVITY= [http://en.wikipedia.org/wiki/Protein-tyrosine-phosphatase Protein-tyrosine-phosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.48 3.1.3.48] | + | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Protein-tyrosine-phosphatase Protein-tyrosine-phosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.48 3.1.3.48] </span> |
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1wax FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1wax OCA], [http://www.ebi.ac.uk/pdbsum/1wax PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1wax 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. | ||
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| - | ==Disease== | ||
| - | Known diseases associated with this structure: Abdominal body fat distribution, modifier of OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176885 176885]], Insulin resistance, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176885 176885]] | ||
==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: LO1]] | ||
| - | [[Category: MG]] | ||
[[Category: acetylation]] | [[Category: acetylation]] | ||
[[Category: hydrolase]] | [[Category: hydrolase]] | ||
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[[Category: protein tyrosine phosphatase]] | [[Category: protein tyrosine phosphatase]] | ||
| - | ''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
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| , resolution 2.20Å | |||||||
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| Sites: | |||||||
| Ligands: | , | ||||||
| Activity: | Protein-tyrosine-phosphatase, with EC number 3.1.3.48 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
PROTEIN TYROSINE PHOSPHATASE 1B WITH ACTIVE SITE INHIBITOR
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
1WAX is a Single protein structure of sequence 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
