Binary complex of calf spleen purine nucleoside phosphorylase with a potent multisubstrate analogue inhibitor
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منابع مشابه
Interactions of calf spleen purine nucleoside phosphorylase with 8-azaguanine, and a bisubstrate analogue inhibitor: implications for the reaction mechanism.
Interactions of calf spleen purine nucleoside phosphorylase (PNP) with a non-typical substrate, 8-azaguanine (8-azaG), and a bisubstrate analogue inhibitor, 9-(2-phosphonylmethoxyethyl)-8-azaguanine (PME-azaG), were investigated by means of steady-state fluorescence spectroscopy. Both 8-azaG and PME-azaG form fluorescent complexes with the enzyme, and dissociation constants are comparable to th...
متن کاملNucleotide analogue inhibitors of purine nucleoside phosphorylase.
The diphosphate of the antiherpetic agent acyclovir [9-[(2-hydroxyethoxy)methyl]guanine] has been shown to inhibit purine nucleoside phosphorylase with unique potency (Tuttle, J. V., and Krenitsky, T. A. (1984) J. Biol. Chem. 259, 4065-4069). A major factor contributing to the superior inhibition by this diphosphate over the corresponding mono- and triphosphates is revealed here. Homologues of ...
متن کاملCalf spleen purine nucleoside phosphorylase complexed with substrates and substrate analogues.
Purine nucleoside phosphorylase (PNP) is a key enzyme in the purine salvage pathway, which provides an alternative to the de novo pathway for the biosynthesis of purine nucleotides. PNP catalyzes the reversible phosphorolysis of 2'-deoxypurine ribonucleosides to the free bases and 2-deoxyribose 1-phosphate. Absence of PNP activity in humans is associated with specific T-cell immune suppression....
متن کاملPurine nucleoside phosphorylase. Kinetic mechanism of the enzyme from calf spleen.
Ribose 1-phosphate, phosphate, and acyclovir diphosphate quenched the fluorescence of purine nucleoside phosphorylase at pH 7.1 and 25 degrees C. The fluorescence of enzyme-bound guanine was similar to that of anionic guanine in ethanol. Guanine and ribose 1-phosphate bound to free enzyme, whereas inosine and guanosine were not bound to free enzyme in the absence of phosphate. Thus, synthesis p...
متن کاملAntiproliferative activity of purine nucleoside phosphorylase multisubstrate analogue inhibitors containing difluoromethylene phosphonic acid against leukaemia and lymphoma cells.
Potent inhibitors of purine nucleoside phosphorylase (PNP) are expected to act as selective agents against T-cell tumours. Five compounds with guanine, three with hypoxanthine, and five with 9-deazaguanine, all connected by a linker with difluoromethylene phosphonic acid, were studied on their inhibitory potential against human and calf PNPs. Antiproliferative activity of these analogues agains...
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ژورنال
عنوان ژورنال: Acta Crystallographica Section A Foundations of Crystallography
سال: 2004
ISSN: 0108-7673
DOI: 10.1107/s0108767304096643