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From Proteopedia
APPLICATION OF CRYSTALLOGRAPHIC AND MODELING METHODS IN THE DESIGN OF PURINE NUCLEOSIDE PHOSPHORYLASE INHIBITORS
Structural highlights
Disease[PNPH_HUMAN] Defects in PNP are the cause of purine nucleoside phosphorylase deficiency (PNPD) [MIM:613179]. It leads to a severe T-cell immunodeficiency with neurologic disorder in children.[1] [2] [3] Function[PNPH_HUMAN] The purine nucleoside phosphorylases catalyze the phosphorolytic breakdown of the N-glycosidic bond in the beta-(deoxy)ribonucleoside molecules, with the formation of the corresponding free purine bases and pentose-1-phosphate.[4] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedCompetitive inhibitors of the salvage pathway enzyme purine-nucleoside phosphorylase (purine-nucleoside:orthophosphate ribosyltransferase, EC 2.4.2.1) have been designed by using the three-dimensional structure of the enzyme as determined by x-ray crystallography. The process was an iterative one that utilized interactive computer graphics, Monte Carlo-based conformational searching, energy minimization, and x-ray crystallography. The proposed compounds were synthesized and tested by an in vitro assay. Among the compounds designed and synthesized are the most potent competitive inhibitors of purine nucleoside phosphorylase thus far reported. Application of crystallographic and modeling methods in the design of purine nucleoside phosphorylase inhibitors.,Ealick SE, Babu YS, Bugg CE, Erion MD, Guida WC, Montgomery JA, Secrist JA 3rd Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11540-4. PMID:1763067[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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