A preliminary neutron diffraction study of rasburicase, a recombinant urate oxidase enzyme, complexed with 8-azaxanthin

Acta Crystallographica. Section F, Structural Biology and Crystallization Communications
M Budayova-SpanoBertrand Castro

Abstract

Crystallization and preliminary neutron diffraction measurements of rasburicase, a recombinant urate oxidase enzyme expressed by a genetically modified Saccharomyces cerevisiae strain, complexed with a purine-type inhibitor (8-azaxanthin) are reported. Neutron Laue diffraction data were collected to 2.1 A resolution using the LADI instrument from a crystal (grown in D2O) with volume 1.8 mm3. The aim of this neutron diffraction study is to determine the protonation states of the inhibitor and residues within the active site. This will lead to improved comprehension of the enzymatic mechanism of this important enzyme, which is used as a protein drug to reduce toxic uric acid accumulation during chemotherapy. This paper illustrates the high quality of the neutron diffraction data collected, which are suitable for high-resolution structural analysis. In comparison with other neutron protein crystallography studies to date in which a hydrogenated protein has been used, the volume of the crystal was relatively small and yet the data still extend to high resolution. Furthermore, urate oxidase has one of the largest primitive unit-cell volumes (space group I222, unit-cell parameters a = 80, b = 96, c = 106 A) and molecular weights (135...Continue Reading

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Citations

Aug 10, 2006·European Biophysics Journal : EBJ·Flora MeilleurMatthew P Blakeley
Dec 24, 2011·Acta Crystallographica. Section D, Biological Crystallography·Parthapratim MunshiFlora Meilleur
Dec 22, 2006·Acta Crystallographica. Section F, Structural Biology and Crystallization Communications·Marc-Michael BlumJulian C-H Chen
May 6, 2008·Acta Crystallographica. Section F, Structural Biology and Crystallization Communications·Susana C M TeixeiraV Trevor Forsyth
Mar 4, 2009·Acta Crystallographica. Section F, Structural Biology and Crystallization Communications·Ricardo M F LealV Trevor Forsyth
Nov 26, 2015·Archives of Biochemistry and Biophysics·William B O'DellFlora Meilleur
Mar 3, 2009·Bioorganic & Medicinal Chemistry·Grzegorz MedzaDavid Shugar
Jul 29, 2008·Current Opinion in Structural Biology·Matthew P BlakeleyAlberto Podjarny
Apr 3, 2013·Current Protocols in Protein Science·John F AnknerDean A A Myles
Jul 21, 2020·Journal of Applied Crystallography·Niels JuniusMonika Budayova-Spano

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