Fine print in isotope effects: the glucose anomeric equilibrium and binding of glucose to human brain hexokinase

• Autorzy: Lewis B. E. , Schramm V. L.
• Konferencja: Proceedings of the International Conference “2001 an Isotope Odyssey: New Application for a New Millenium", June 24-29, 2001, Zakopane, Poland
• Języki publikacji: EN

Abstrakty

EN

Binding isotope effects are a sensitive measure of changes in molecular vibrational character that occur during ligand- receptor binding. In this study, we have measured isotope effects on the binding of glucose to human brain hexokinase using the ultrafiltration method, with the following results: 0.991š0.001, 0.908š0.003, 1.010š0.001, 0.974š0.002, 1.022š0.002 for [14C]-glucose mixed with [1-3H]-, [2-3H]-, [3-3H]-, [5-3H]-, [6,6-3H2]-glucose, respectively. Comparing the observed data with isotope effects on the anomeric equilibrium in glucose reported previously [3] proves the existence of binding isotope effects in this system. Preliminary computational results are presented to explain the observed binding isotope effects in terms of hydrogen bond patterns and molecular crowding found in the binary complex of sugar and enzyme.

Słowa kluczowe

EN

anomeric equilibrium; binding isotope effects; computational chemistry; conformational equilibrium isotope effects; glucose; hexokinase

• Wydawca: Institute of Nuclear Chemistry and Technology
• Czasopismo: Nukleonika
• Rocznik: 2002
• Tom: Vol. 47,suppl.1
• Strony: 3--7
• Opis fizyczny: Bibliogr. 4 poz., rys.

Twórcy

autor

Lewis B. E.

• The Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, New York 10461, USA, Tel.: [phone], Fax: [phone]

autor

Schramm V. L.

• The Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, New York 10461, USA, Tel.: [phone], Fax: [phone]

Bibliografia

• 1. Aleshin AE, Zeng C, Bourenkov GP, Bartunik HD, Fromm HJ, Honzatko RB (1998) The mechanism of regulation of hexokinase: new insights from the crystal structure of recombinant human brain hexokinase complexed with glucose and glucose-6-phosphate. Structure 6:39–50
• 2. Lemieux RU, Chu NJ (1958) Conformations and relative stabilities of acetylated sugars as determined by nuclear magnetic resonance spectroscopy and anomerization equilibria. Am Chem Soc 133:31N
• 3. Lewis BE, Schramm VL (2001) Conformational equilibrium isotope effects in glucose by 13C-NMR spectroscopy and computational studies. J Am Chem Soc 123:1327–1336
• 4. Rose IA, O’Connell EL, Litwin S (1974) Determination of the rate of hexokinase-glucose dissociation by the isotope-trapping method. J Biol Chem 249:5163–5168