L-Enantiomers of transition state analogue inhibitors bound to human purine nucleoside phosphorylase.
Human purine nucleoside phosphorylase (PNP) was crystallized with transition-state analogue inhibitors Immucillin-H and DADMe-Immucillin-H synthesized with ribosyl mimics of l-stereochemistry. The inhibitors demonstrate that major driving forces for tight binding of these analogues are the leaving group interaction and the cationic mimicry of the transition state, even though large geometric changes occur with d-Immucillins and l-Immucillins bound to human PNP.
D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000737:chemistry*; D006801:Humans; D011487:Protein Conformation; D011684:Purine Nucleosides / Q000737:chemistry*; D011683:Purine-Nucleoside Phosphorylase / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D011744:Pyrimidinones / Q000737:chemistry*; D011759:Pyrrolidines / Q000737:chemistry*; D013237:Stereoisomerism; D013379:Substrate Specificity
C508755:DADMe-immucillin H; D004791:Enzyme Inhibitors; D011684:Purine Nucleosides; D011744:Pyrimidinones; D011759:Pyrrolidines; C113101:forodesine; D011683:Purine-Nucleoside Phosphorylase