1db5
HUMAN S-PLA2 IN COMPLEX WITH INDOLE 6
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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 with and as ligands. Active as Phospholipase A(2), with EC number 3.1.1.4 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
Page seeded by OCA on Thu Feb 21 12:14:49 2008