1db4: Difference between revisions
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|PDB= 1db4 |SIZE=350|CAPTION= <scene name='initialview01'>1db4</scene>, resolution 2.20Å | |PDB= 1db4 |SIZE=350|CAPTION= <scene name='initialview01'>1db4</scene>, resolution 2.20Å | ||
|SITE= | |SITE= | ||
|LIGAND= | |LIGAND= <scene name='pdbligand=8IN:[3-(1-BENZYL-3-CARBAMOYLMETHYL-2-METHYL-1H-INDOL-5-YLOXY)-PROPYL-]-PHOSPHONIC+ACID'>8IN</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene> | ||
|ACTIVITY= [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] | |ACTIVITY= <span class='plainlinks'>[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] </span> | ||
|GENE= | |GENE= | ||
|DOMAIN= | |||
|RELATEDENTRY=[[1db5|1DB5]], [[1dcy|1DCY]] | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1db4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1db4 OCA], [http://www.ebi.ac.uk/pdbsum/1db4 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1db4 RCSB]</span> | |||
}} | }} | ||
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==Overview== | ==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. | 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. | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Schevitz, R W.]] | [[Category: Schevitz, R W.]] | ||
[[Category: Wery, J P.]] | [[Category: Wery, J P.]] | ||
[[Category: hydrolase/hydrolase inhibitor]] | [[Category: hydrolase/hydrolase inhibitor]] | ||
[[Category: s-pla2]] | [[Category: s-pla2]] | ||
[[Category: structure-based drug design]] | [[Category: structure-based drug design]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 19:38:08 2008'' | ||
