1wok
From Proteopedia
(New page: 200px<br /> <applet load="1wok" size="450" color="white" frame="true" align="right" spinBox="true" caption="1wok, resolution 3.00Å" /> '''Crystal structure o...) |
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| - | [[Image:1wok.gif|left|200px]]<br /> | + | [[Image:1wok.gif|left|200px]]<br /><applet load="1wok" size="350" color="white" frame="true" align="right" spinBox="true" |
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caption="1wok, resolution 3.00Å" /> | caption="1wok, resolution 3.00Å" /> | ||
'''Crystal structure of catalytic domain of human poly(ADP-ribose) polymerase complexed with a quinoxaline-type inhibitor'''<br /> | '''Crystal structure of catalytic domain of human poly(ADP-ribose) polymerase complexed with a quinoxaline-type inhibitor'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Two classes of quinazolinone derivatives and quinoxaline derivatives were | + | Two classes of quinazolinone derivatives and quinoxaline derivatives were identified as potent and selective poly(ADP-ribose) polymerase-1 and 2 (PARP-1) and (PARP-2) inhibitors, respectively. In PARP enzyme assays using recombinant PARP-1 and PARP-2, quinazolinone derivatives displayed relatively high selectivity for PARP-1 and quinoxaline derivatives showed superior selectivity for PARP-2. SBDD analysis via a combination of X-ray structural study and homology modeling suggested distinct interactions of inhibitors with PARP-1 and PARP-2. These findings provide a new structural framework for the design of selective inhibitors for PARP-1 and PARP-2. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1WOK is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with CNQ as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [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] Full crystallographic information is available from [http:// | + | 1WOK is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=CNQ:'>CNQ</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1WOK OCA]. |
==Reference== | ==Reference== | ||
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[[Category: protein-inhibitor complex]] | [[Category: protein-inhibitor complex]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:46:34 2008'' |
Revision as of 13:46, 21 February 2008
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Crystal structure of catalytic domain of human poly(ADP-ribose) polymerase complexed with a quinoxaline-type inhibitor
Contents |
Overview
Two classes of quinazolinone derivatives and quinoxaline derivatives were identified as potent and selective poly(ADP-ribose) polymerase-1 and 2 (PARP-1) and (PARP-2) inhibitors, respectively. In PARP enzyme assays using recombinant PARP-1 and PARP-2, quinazolinone derivatives displayed relatively high selectivity for PARP-1 and quinoxaline derivatives showed superior selectivity for PARP-2. SBDD analysis via a combination of X-ray structural study and homology modeling suggested distinct interactions of inhibitors with PARP-1 and PARP-2. These findings provide a new structural framework for the design of selective inhibitors for PARP-1 and PARP-2.
Disease
Known diseases associated with this structure: Xeroderma pigmentosum (1) OMIM:[173870]
About this Structure
1WOK is a Single protein structure of sequence from Homo sapiens with as ligand. Active as NAD(+) ADP-ribosyltransferase, with EC number 2.4.2.30 Full crystallographic information is available from OCA.
Reference
Discovery of quinazolinone and quinoxaline derivatives as potent and selective poly(ADP-ribose) polymerase-1/2 inhibitors., Iwashita A, Hattori K, Yamamoto H, Ishida J, Kido Y, Kamijo K, Murano K, Miyake H, Kinoshita T, Warizaya M, Ohkubo M, Matsuoka N, Mutoh S, FEBS Lett. 2005 Feb 28;579(6):1389-93. PMID:15733846
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