1db4
From Proteopedia
(New page: 200px<br /> <applet load="1db4" size="450" color="white" frame="true" align="right" spinBox="true" caption="1db4, resolution 2.20Å" /> '''HUMAN S-PLA2 IN COM...) |
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| - | [[Image:1db4.gif|left|200px]]<br /> | + | [[Image:1db4.gif|left|200px]]<br /><applet load="1db4" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1db4" size=" | + | |
caption="1db4, resolution 2.20Å" /> | caption="1db4, resolution 2.20Å" /> | ||
'''HUMAN S-PLA2 IN COMPLEX WITH INDOLE 8'''<br /> | '''HUMAN S-PLA2 IN COMPLEX WITH INDOLE 8'''<br /> | ||
==Overview== | ==Overview== | ||
| - | A lead compound obtained from a high volume human non-pancreatic secretory | + | A lead compound obtained from a high volume human non-pancreatic secretory phospholipase A2 (hnps-PLA2) screen has been developed into a potent inhibitor using detailed structural knowledge of inhibitor binding to the enzyme active site. Four crystal structures of hnps-PLA2 complexed with a series of increasingly potent indole inhibitors were determined and used as the structural basis for both understanding this binding and providing valuable insights for further development. The application of structure-based drug design has made possible improvements in the binding of this screening lead to the enzyme by nearly three orders of magnitude. Furthermore, the optimized structure (LY311727) displayed 1,500-fold selectivity when assayed against porcine pancreatic s-PLA2. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1DB4 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 CA and 8IN as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Phospholipase_A(2) Phospholipase A(2)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.1.4 3.1.1.4] Full crystallographic information is available from [http:// | + | 1DB4 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=CA:'>CA</scene> and <scene name='pdbligand=8IN:'>8IN</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Phospholipase_A(2) Phospholipase A(2)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.1.4 3.1.1.4] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1DB4 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Phospholipase A(2)]] | [[Category: Phospholipase A(2)]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Chirgadze, N | + | [[Category: Chirgadze, N Y.]] |
| - | [[Category: Schevitz, R | + | [[Category: Schevitz, R W.]] |
| - | [[Category: Wery, J | + | [[Category: Wery, J P.]] |
[[Category: 8IN]] | [[Category: 8IN]] | ||
[[Category: CA]] | [[Category: CA]] | ||
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[[Category: structure-based drug design]] | [[Category: structure-based drug design]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:14:51 2008'' |
Revision as of 10:14, 21 February 2008
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HUMAN S-PLA2 IN COMPLEX WITH INDOLE 8
Contents |
Overview
A lead compound obtained from a high volume human non-pancreatic secretory phospholipase A2 (hnps-PLA2) screen has been developed into a potent inhibitor using detailed structural knowledge of inhibitor binding to the enzyme active site. Four crystal structures of hnps-PLA2 complexed with a series of increasingly potent indole inhibitors were determined and used as the structural basis for both understanding this binding and providing valuable insights for further development. The application of structure-based drug design has made possible improvements in the binding of this screening lead to the enzyme by nearly three orders of magnitude. Furthermore, the optimized structure (LY311727) displayed 1,500-fold selectivity when assayed against porcine pancreatic s-PLA2.
Disease
Known diseases associated with this structure: Colorectal cancer, sporadic OMIM:[172411]
About this Structure
1DB4 is a Single protein structure of sequence from Homo sapiens with and as ligands. Active as Phospholipase A(2), with EC number 3.1.1.4 Full crystallographic information is available from OCA.
Reference
Structure-based design of the first potent and selective inhibitor of human non-pancreatic secretory phospholipase A2., Schevitz RW, Bach NJ, Carlson DG, Chirgadze NY, Clawson DK, Dillard RD, Draheim SE, Hartley LW, Jones ND, Mihelich ED, et al., Nat Struct Biol. 1995 Jun;2(6):458-65. PMID:7664108
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