Universität zu Köln

Belaidi, Abdel A., Roeper, Juliane, Arjune, Sita, Krizowski, Sabina, Trifunovic, Aleksandra and Schwarz, Guenter ORCID: 0000-0002-2118-9338 (2015). Oxygen reactivity of mammalian sulfite oxidase provides a concept for the treatment of sulfite oxidase deficiency. Biochem. J., 469. S. 211 - 222. LONDON: PORTLAND PRESS LTD. ISSN 1470-8728

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Abstract

Mammalian sulfite oxidase (SO) is a dimeric enzyme consisting of a molybdenum cofactor-(Moco) and haem-containing domain and catalyses the oxidation of toxic sulfite to sulfate. Following sulfite oxidation, electrons are passed from Moco via the haem cofactor to cytochrome c, the terminal electron acceptor. In contrast, plant SO (PSO) lacks the haem domain and electrons shuttle from Moco to molecular oxygen. Given the high similarity between plant and mammalian SO Moco domains, factors that determine the reactivity of PSO towards oxygen, remained unknown. In the present study, we generated mammalian haem-deficient and truncated SO variants and demonstrated their oxygen reactivity by hydrogen peroxide formation and oxygen-consumption studies. We found that intramolecular electron transfer between Moco and haem showed an inverse correlation to SO oxygen reactivity. Haem-deficient SO variants exhibited oxygen-dependent sulfite oxidation similar to PSO, which was confirmed further using haem-deficient human SO in a cell-based assay. This finding suggests the possibility to use oxygen-reactive SO variants in sulfite detoxification, as the loss of SO activity is causing severe neurodegeneration. Therefore we evaluated the potential use of PEG attachment (PEGylation) as a modification method for future enzyme substitution therapies using oxygen-reactive SO variants, which might use blood-dissolved oxygen as the electron acceptor. PEGylation has been shown to increase the half-life of other therapeutic proteins. PEGylation resulted in the modification of up to eight surface-exposed lysine residues of SO, an increased conformational stability and similar kinetic properties compared with wild-type SO.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Belaidi, Abdel A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Roeper, Juliane UNSPECIFIED UNSPECIFIED UNSPECIFIED Arjune, Sita UNSPECIFIED UNSPECIFIED UNSPECIFIED Krizowski, Sabina UNSPECIFIED UNSPECIFIED UNSPECIFIED Trifunovic, Aleksandra UNSPECIFIED UNSPECIFIED UNSPECIFIED Schwarz, Guenter UNSPECIFIED orcid.org/0000-0002-2118-9338 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-398773
DOI:	10.1042/BJ20140768
Journal or Publication Title:	Biochem. J.
Volume:	469
Page Range:	S. 211 - 222
Date:	2015
Publisher:	PORTLAND PRESS LTD
Place of Publication:	LONDON
ISSN:	1470-8728
Language:	English
Faculty:	Faculty of Mathematics and Natural Sciences
Divisions:	Faculty of Mathematics and Natural Sciences > Department of Chemistry > Institute of Biochemistry
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language MOLYBDENUM COFACTOR DEFICIENCY; INTRAMOLECULAR ELECTRON-TRANSFER; PULSED EPR SPECTROSCOPY; ARABIDOPSIS-THALIANA; OXIDIZING ENZYMES; HEPATITIS-C; MUTATIONS; CATALYSIS; FORM; PURIFICATION Multiple languages Biochemistry & Molecular Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/39877