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Crystal structure of calf spleen purine nucleoside phosphorylase complexed to a novel purine analogue
Author(s) -
Pereira H.M.,
Berdini V.,
Cleasby A.,
Garratt R.C.
Publication year - 2007
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2007.09.051
Subject(s) - purine nucleoside phosphorylase , chemistry , nucleotide salvage , purine , ligand (biochemistry) , stereochemistry , enzyme , purine metabolism , nucleoside , crystal (programming language) , nucleotide , crystallography , biochemistry , receptor , gene , computer science , programming language
The combined use of a rapid virtual screen of a small fragment library together with a single point enzyme assay has been used for the discovery of novel PNP inhibitors. The availability of readily soakable crystals of bovine PNP has allowed the approach to be experimentally validated by determining the crystal structure of one of the inhibitor‐PNP complexes. Comparison of the experimentally determined binding mode with that predicted by the virtual screening shows them to be similar. This represents a starting point for the growth of the ligand into a higher affinity inhibitor.