Characterization of hydrogen bonding in the complex of adenosine deaminase with a transition state analogue: a Raman spectroscopic study

Biochemistry
Hua DengRobert Callender

Abstract

The Raman spectra of purine ribonucleoside as well as a stable model compound (1-methoxyl-1,6-dihydropurine ribonucleoside), free in solution and bound into its complex with adenosine deaminase (ADA), have been studied by Raman difference spectroscopy. Using purine riboside analogues labeled with 15N1 or 13C6 and the theoretical frequency normal-mode analyses of these molecules using ab initio quantum mechanic methods, we have positively identified many of the Raman bands in the enzyme-bound inhibitor. The spectrum of the enzyme-bound inhibitor is consistent with the enzyme-catalyzed hydration of the purine base to yield 1-hydroxyl-1,6-dihydropurine ribonucleoside, as suggested earlier by X-ray crystallographic studies. In addition, the Raman data and subsequent vibrational analyses show that the binding-induced Raman spectral changes of the inhibitor can be modeled by the formation of a strong hydrogen bond to its N1-H bond. This hydrogen bond, apparently between the N1-H of the inhibitor and the Odelta1 of Glu217 in ADA, causes a substantial N1-H bending frequency increase of about 50-100 cm-1 compared to its solution value, and this results in an estimated enthalpy of the hydrogen bond of 4-10 kcal/mol. The relationship of t...Continue Reading

Citations

Mar 17, 2007·Nucleosides, Nucleotides & Nucleic Acids·Avital LaxerBilha Fischer
Jul 20, 1999·Annual Review of Biophysics and Biomolecular Structure·G J Thomas
Aug 16, 2014·Molecular BioSystems·Jacek WierzchowskiDavid Shugar
Jul 15, 2015·Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy·Vishakha Karnawat, Mrinalini Puranik
Sep 10, 1999·The Journal of Biological Chemistry·P R Carey
Jul 15, 2000·The Journal of Biological Chemistry·H DengG E Dale

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