L-Enantiomers of Transition State Analogue Inhibitors Bound to Human Purine Nucleoside Phosphorylase

Journal Article · Tue Jan 01 04:00:00 EST 2008 · Journal of the American Chemical Society

DOI:https://doi.org/10.1021/ja710733g· OSTI ID:959777

Rinaldo-Matthis, A; Murkin, A; Ramagopal, U; Clinch, K; Mee, S; Evans, G; Tyler, P; Furneaux, R; Almo, S; Schramm, v

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.

• Research Organization: Brookhaven National Laboratory (BNL) National Synchrotron Light Source
• Sponsoring Organization: Doe - Office Of Science
• DOE Contract Number: AC02-98CH10886
• OSTI ID: 959777
• Report Number(s): BNL--82763-2009-JA
• Journal Information: Journal of the American Chemical Society, Journal Name: Journal of the American Chemical Society Vol. 130; ISSN JACSAT; ISSN 0002-7863
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
99 GENERAL AND MISCELLANEOUS
NUCLEOSIDES
PHOSPHOTRANSFERASES
PURINES
STEREOCHEMISTRY
national synchrotron light source