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![[Figure 1]](xh5067fig1mag.jpg)
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Figure 1
UOX-catalysed reaction and peroxide radiolysis. (a) UOX catalyses the O2- and H2O-dependent conversion of uric acid (UA), present predominantly in its monoanionic form at physiological pH, to 5-hydroxyisourate (5-HIU). The first step of the reaction proceeds via formation of the 5-peroxyisourate (5-PIU) intermediate. (b) Chemical structure of 9-methyl uric acid (MUA), the alternative substrate used in this work. MUA undergoes oxygenation to form its 5-peroxy derivative [5-hydroperoxy-(9-methyl)-8-oxy-5,9-dihydro-1H-purine-2,6-dione, 5-PMUA], but unlike 5-PIU it is unable to advance further in the catalytic mechanism as it lacks the hydrogen at position 9. Here and in (a), the five-membered ring of the substrate is shown in its lactim form as indicated by neutron diffraction studies of the aerobic chloride-inhibited UOX–UA complex (Oksanen et al., 2014  ). (c) Both peroxides (the R substituent at position 9 is H in UA, whilst it is CH3 in MUA) are easily radiolysed during X-ray data collection. Following radiation-induced damage (RADDAM) under cryogenic conditions, O2 remains trapped in the `peroxo-hole' in close proximity to the organic moiety, which is believed to be a stable UA/MUA radical. A mechanism of partial 5-PMUA regeneration is believed to be operational alongside the RADDAM process (Bui et al., 2014). In all panels, the C5—OO(H) bond that is selectively broken/formed is shown in red. |
![[Figure 1]](xh5067fig1.jpg)
 | STRUCTURAL BIOLOGY |
ISSN: 2059-7983
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