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PDBsum entry 1db5
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Hydrolase/hydrolase inhibitor
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PDB id
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1db5
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Structure-Based design of the first potent and selective inhibitor of human non-Pancreatic secretory phospholipase a2.
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Authors
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R.W.Schevitz,
N.J.Bach,
D.G.Carlson,
N.Y.Chirgadze,
D.K.Clawson,
R.D.Dillard,
S.E.Draheim,
L.W.Hartley,
N.D.Jones,
E.D.Mihelich.
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Ref.
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Nat Struct Biol, 1995,
2,
458-465.
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PubMed id
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Abstract
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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.
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