1db4
From Proteopedia
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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. | ||
| - | |||
| - | ==Disease== | ||
| - | Known diseases associated with this structure: Colorectal cancer, sporadic OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=172411 172411]] | ||
==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: 8IN]] | ||
| - | [[Category: CA]] | ||
[[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'' |
Revision as of 16:38, 30 March 2008
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| , resolution 2.20Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , | ||||||
| Activity: | Phospholipase A(2), with EC number 3.1.1.4 | ||||||
| Related: | 1DB5, 1DCY
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
HUMAN S-PLA2 IN COMPLEX WITH INDOLE 8
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.
About this Structure
1DB4 is a Single protein structure of sequence from Homo sapiens. 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
Page seeded by OCA on Sun Mar 30 19:38:08 2008
