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1uk1
From Proteopedia
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|SITE= | |SITE= | ||
|LIGAND= <scene name='pdbligand=FRQ:5-FLUORO-1-[4-(4-PHENYL-3,6-DIHYDROPYRIDIN-1(2H)-YL)BUTYL]QUINAZOLINE-2,4(1H,3H)-DIONE'>FRQ</scene> | |LIGAND= <scene name='pdbligand=FRQ:5-FLUORO-1-[4-(4-PHENYL-3,6-DIHYDROPYRIDIN-1(2H)-YL)BUTYL]QUINAZOLINE-2,4(1H,3H)-DIONE'>FRQ</scene> | ||
| - | |ACTIVITY= [http://en.wikipedia.org/wiki/NAD(+)_ADP-ribosyltransferase NAD(+) ADP-ribosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.30 2.4.2.30] | + | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/NAD(+)_ADP-ribosyltransferase NAD(+) ADP-ribosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.30 2.4.2.30] </span> |
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1uk0|1UK0]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1uk1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1uk1 OCA], [http://www.ebi.ac.uk/pdbsum/1uk1 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1uk1 RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==Overview== | ||
A novel class of quinazolinone derivatives as potent poly(ADP-ribose)polymerase-1 (PARP-1) inhibitors has been discovered. Key to success was application of a rational discovery strategy involving structure-based design, combinatorial chemistry, and classical SAR for improvement of potency and bioavailability. The new inhibitors were shown to bind to the nicotinamide-ribose binding site (NI site) and the adenosine-ribose binding site (AD site) of NAD+. | A novel class of quinazolinone derivatives as potent poly(ADP-ribose)polymerase-1 (PARP-1) inhibitors has been discovered. Key to success was application of a rational discovery strategy involving structure-based design, combinatorial chemistry, and classical SAR for improvement of potency and bioavailability. The new inhibitors were shown to bind to the nicotinamide-ribose binding site (NI site) and the adenosine-ribose binding site (AD site) of NAD+. | ||
| - | |||
| - | ==Disease== | ||
| - | Known diseases associated with this structure: Xeroderma pigmentosum (1) OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=173870 173870]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Kinoshita, T.]] | [[Category: Kinoshita, T.]] | ||
| - | [[Category: FRQ]] | ||
[[Category: protein-inhibitor complex]] | [[Category: protein-inhibitor complex]] | ||
| - | ''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 00:11:18 2008'' |
Revision as of 21:11, 30 March 2008
| |||||||
| , resolution 3.Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Activity: | NAD(+) ADP-ribosyltransferase, with EC number 2.4.2.30 | ||||||
| Related: | 1UK0
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of human poly(ADP-ribose) polymerase complexed with a potent inhibitor
Overview
A novel class of quinazolinone derivatives as potent poly(ADP-ribose)polymerase-1 (PARP-1) inhibitors has been discovered. Key to success was application of a rational discovery strategy involving structure-based design, combinatorial chemistry, and classical SAR for improvement of potency and bioavailability. The new inhibitors were shown to bind to the nicotinamide-ribose binding site (NI site) and the adenosine-ribose binding site (AD site) of NAD+.
About this Structure
1UK1 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Rational approaches to discovery of orally active and brain-penetrable quinazolinone inhibitors of poly(ADP-ribose)polymerase., Hattori K, Kido Y, Yamamoto H, Ishida J, Kamijo K, Murano K, Ohkubo M, Kinoshita T, Iwashita A, Mihara K, Yamazaki S, Matsuoka N, Teramura Y, Miyake H, J Med Chem. 2004 Aug 12;47(17):4151-4. PMID:15293985
Page seeded by OCA on Mon Mar 31 00:11:18 2008
