109309-22-0Relevant articles and documents
Structural studies of the molybdenum center of the pathogenic R160Q mutant of human sulfite oxidase by pulsed EPR spectroscopy and 17O and 33S labeling
Astashkin, Andrei V.,Johnson-Winters, Kayunta,Klein, Eric L.,Feng, Changjian,Wilson, Heather L.,Rajagopalan,Raitsimring, Arnold M.,Enemark, John H.
, p. 8471 - 8480 (2008)
Electron paramagnetic resonance (EPR) investigation of the Mo(V) center of the pathogenic R16OQ mutant of human sulfite oxidase (hSO) confirms the presence of three distinct species whose relative abundances depend upon pH. Species 1 is exclusively present at pH ≤ 6, and remains in significant amounts even at pH 8. Variable-frequency electron spin echo envelope modulation (ESEEM) studies of this species prepared with 33S-labeled sulfite clearly show the presence of coordinated sulfate, as has previously been found for the blocked form of Arabidopsis thaliana at low pH (Astashkin, A. V.; Johnson-Winters, K.; Klein, E. L.; Byrne, R. S.; Hille, R.; Raitsimring, A. M.; Enemark, J. H. J. Am. Chem. Soc. 2007, 129, 14800). The ESEEM spectra of Species 1 prepared in 17O-enriched water show both strongly and weakly magnetically coupled 17O atoms that can be assigned to an equatorial sulfate ligand and the axial oxo ligand, respectively. The nuclear quadrupole interaction (nqi) of the axial oxo ligand is substantially stronger than those found for other oxo-Mo(V) centers studied previously. Additionally, pulsed electron-nuclear double resonance (ENDOR) measurements reveal a nearby weakly coupled exchangeable proton. The structure for Species 1 proposed from the pulsed EPR results using isotopic labeling is a six-coordinate Mo(V) center with an equatorial sulfate ligand that is hydrogen bonded to an exchangeable proton. Six-coordination is supported by the 17O nqi parameters for the axial oxo group of the model compound, (dttd)Mo17O( 17Otms), where H2dttd = 2,3:8,9-dibenzo-1,4,7,10- tetrathiadecane; tms = trimethylsilyl. Reduction of R160Q to Mo(V) with Ti(III) gives primarily Species 2, another low pH form, whereas reduction with sulfite at higher pH values gives a mixture of Species 1 and 2, as well as the primary high pH form of wild-type SO. The occurrence of significant amounts of the sulfate-blocked form of R160Q (Species 1) at physiological pH suggests that this species may be a contributing factor to the lethality of this mutation.
