1db5: Difference between revisions
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[[Image:1db5.gif|left|200px]] | [[Image:1db5.gif|left|200px]] | ||
'''HUMAN S-PLA2 IN COMPLEX WITH INDOLE 6''' | {{Structure | ||
|PDB= 1db5 |SIZE=350|CAPTION= <scene name='initialview01'>1db5</scene>, resolution 2.80Å | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene> and <scene name='pdbligand=6IN:4-(1-BENZYL-3-CARBAMOYLMETHYL-2-METHYL-1H-INDOL-5-YLOXY)-BUTYRIC ACID'>6IN</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] | |||
|GENE= | |||
}} | |||
'''HUMAN S-PLA2 IN COMPLEX WITH INDOLE 6''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
1DB5 is a [ | 1DB5 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1DB5 OCA]. | ||
==Reference== | ==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:[http:// | 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:[http://www.ncbi.nlm.nih.gov/pubmed/7664108 7664108] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Phospholipase A(2)]] | [[Category: Phospholipase A(2)]] | ||
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[[Category: s-pla2; structure-based drug design]] | [[Category: s-pla2; structure-based drug design]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 10:35:39 2008'' | ||
Revision as of 11:35, 20 March 2008
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| , resolution 2.80Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | and | ||||||
| Activity: | Phospholipase A(2), with EC number 3.1.1.4 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
HUMAN S-PLA2 IN COMPLEX WITH INDOLE 6
OverviewOverview
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.
DiseaseDisease
Known diseases associated with this structure: Colorectal cancer, sporadic OMIM:[172411]
About this StructureAbout this Structure
1DB5 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
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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