Universität zu Köln

Bender, Daniel ORCID: 0000-0002-2975-4186, Kaczmarek, Alexander Tobias, Niks, Dimitri, Hille, Russ and Schwarz, Guenter ORCID: 0000-0002-2118-9338 (2019). Mechanism of nitrite-dependent NO synthesis by human sulfite oxidase. Biochem. J., 476. S. 1805 - 1816. LONDON: PORTLAND PRESS LTD. ISSN 1470-8728

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Abstract

In addition to nitric oxide (NO) synthases, molybdenum-dependent enzymes have been reported to reduce nitrite to produce NO. Here, we report the stoichiometric reduction in nitrite to NO by human sulfite oxidase (SO), a mitochondrial intermembrane space enzyme primarily involved in cysteine catabolism. Kinetic and spectroscopic studies provide evidence for direct nitrite coordination at the molybdenum center followed by an inner shell electron transfer mechanism. In the presence of the physiological electron acceptor cytochrome c, we were able to close the catalytic cycle of sulfite-dependent nitrite reduction thus leading to steady-state NO synthesis, a finding that strongly supports a physiological relevance of SO-dependent NO formation. By engineering SO variants with reduced intramolecular electron transfer rate, we were able to increase NO generation efficacy by one order of magnitude, providing a mechanistic tool to tune NO synthesis by SO.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Bender, Daniel UNSPECIFIED orcid.org/0000-0002-2975-4186 UNSPECIFIED Kaczmarek, Alexander Tobias UNSPECIFIED UNSPECIFIED UNSPECIFIED Niks, Dimitri UNSPECIFIED UNSPECIFIED UNSPECIFIED Hille, Russ UNSPECIFIED UNSPECIFIED UNSPECIFIED Schwarz, Guenter UNSPECIFIED orcid.org/0000-0002-2118-9338 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-137367
DOI:	10.1042/BCJ20190143
Journal or Publication Title:	Biochem. J.
Volume:	476
Page Range:	S. 1805 - 1816
Date:	2019
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; SYNTHASE ACTIVITY; XANTHINE-OXIDASE; REDUCTASE; NITRATE; DEOXYHEMOGLOBIN; ISCHEMIA; PATHWAY; ENZYMES; INJURY Multiple languages Biochemistry & Molecular Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/13736