Reciprocal regulation of sulfite oxidation and nitrite reduction by mitochondrial sulfite oxidase

Kaczmarek, Alexander Tobias; Strampraad, Marc J. F.; Hagedoorn, Peter‐Leon; Schwarz, Günter

doi:10.1016/j.niox.2019.04.004

Cited by 10 publications

(12 citation statements)

References 67 publications

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“…For SOX/SOX a k1 of 24.8 ± 2.0 s -1 was determined, which is similar to previously reported values (18,19). Furthermore, a k2 of 2.09 ± 0.34 s -1 was observed, which is faster than the inter-molecular rates k3 and k4.…”

Section: Discussionsupporting

confidence: 89%

“…For the pathogenic G530D substitution in SOX, the monomeric state has been demonstrated in vitro (24,25) and we asked the question whether pathogenicity may result from loss of electron bifurcation. This would not only account for the importance of homodimerization but may also explain the different rates observed for the first and second IET, respectively (18,20).…”

Section: Discussionmentioning

confidence: 99%

“…This is highlighted by a recent study that identified 15 novel ISOD-causing missense mutations of which another four localized to the dimerization domain (23). Given that the two metal atoms of the cofactors are too far apart in the crystal structure of chicken SOX to allow efficient IET (6,18,20), it is well accepted that a conformational change occurs, which is mediated by the flexible tether connecting the heme and Moco domain (16,17). However, to date, the IET-competent conformation remains unknown.…”

Section: Discussionmentioning

confidence: 99%

“…While oxidation of sulfite and the concomitant reduction of molybdenum in the reductive half reaction of SOX were measured with 541 s -1 , the first IET from Mo (IV) to the heme-iron were substantially slower with rates of 80 s -1 at pH 7.7 and 28 s -1 at pH 8.0 (18,19). The rates for the second IET within SOX revealed ET rates of up to 700 s -1 from Mo (V) to the iron of heme (20).…”

Section: Introductionmentioning

confidence: 99%

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Molecular mechanism of intramolecular electron transfer in dimeric sulfite oxidase

Eh¹,

Kaczmarek²,

Schwarz³

et al. 2022

Journal of Biological Chemistry

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Molecular mechanism of intramolecular electron transfer in dimeric sulfite oxidase

Eh¹,

Kaczmarek²,

Schwarz³

et al. 2022

Journal of Biological Chemistry

Self Cite

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“…This is enabled by the flexible tether connecting both domains . Alternatively, SO can use nitrite as electron acceptor for sulphite‐derived electrons thereby producing nitric oxide (NO) . Similarly, sulphite‐derived electrons can be shuttled to molecular oxygen (O 2 ) .…”

Section: Introductionmentioning

confidence: 99%

Oxygen and nitrite reduction by heme‐deficient sulphite oxidase in a patient with mild sulphite oxidase deficiency

Bender

Kaczmarek

Kuester

et al. 2020

J of Inher Metab Disea

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Isolated sulphite oxidase deficiency (iSOD) is an autosomal recessive inborn error in metabolism characterised by accumulation of sulphite, which leads to death in early infancy. Sulphite oxidase (SO) is encoded by the SUOX gene and forms a heme‐ and molybdenum‐cofactor‐dependent enzyme localised in the intermembrane space of mitochondria. Within SO, both cofactors are embedded in two separated domains, which are linked via a flexible 11 residue tether. The two‐electron oxidation of sulphite to sulphate occurs at the molybdenum active site. From there, electrons are transferred via two intramolecular electron transfer steps (IETs) via the heme cofactor and to the physiologic electron acceptor cytochrome c. Previously, we reported nitrite and oxygen to serve as alternative electron acceptors at the Moco active site, thereby overcoming IET within SO. Here, we present evidence for these reactions to occur in an iSOD patient with an unusual mild disease representation. In the patient, a homozygous c.427C>A mutation within the SUOX gene leads to replacement of the highly conserved His143 to Asn. The affected His143 is one of two heme‐iron‐coordinating residues within SO. We demonstrate, that the H143N SO variant fails to bind heme in vivo leading to the elimination of SO‐dependent cytochrome c reduction in mitochondria. We show, that sulphite oxidation at the Moco domain is unaffected in His143Asn SO variant and demonstrate that nitrite and oxygen are able to serve as electron acceptors for sulphite‐derived electrons in cellulo. As result, the patient H143N SO variant retains residual sulphite oxidising activity thus ameliorating iSOD progression.

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Selective Oxyfunctionalisation Reactions Driven by Sulfite Oxidase‐Catalysed In Situ Generation of H₂O₂

et al. 2020

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H2O2 can be accepted by several peroxygenases as a clean oxidant, able to supply both the necessary electrons and oxygen atom at the same time. The biocatalysts, in turn, are able to catalyse an array of interesting oxygen insertion reactions at enantio‐ and regio‐selectivities hard to attain with classical chemical methods. The sensitivity of most peroxygenases towards H2O2, however, requires this oxidant to be generated in situ. Here, we suggest the application of (modified) sulfite oxidases to couple the oxidation of sulfites to the reduction of oxygen. This enables us to use calcium sulfite, an industrial waste product from scrubbing flue gases, as an electron donor to reduce oxygen. This will supply the required peroxide in a controlled manner and enables us to perform these challenging reactions at the expense of simple salts.

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Reciprocal regulation of sulfite oxidation and nitrite reduction by mitochondrial sulfite oxidase

Cited by 10 publications

References 67 publications

Molecular mechanism of intramolecular electron transfer in dimeric sulfite oxidase

Molecular mechanism of intramolecular electron transfer in dimeric sulfite oxidase

Oxygen and nitrite reduction by heme‐deficient sulphite oxidase in a patient with mild sulphite oxidase deficiency

Selective Oxyfunctionalisation Reactions Driven by Sulfite Oxidase‐Catalysed In Situ Generation of H₂O₂

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Reciprocal regulation of sulfite oxidation and nitrite reduction by mitochondrial sulfite oxidase

Cited by 10 publications

References 67 publications

Molecular mechanism of intramolecular electron transfer in dimeric sulfite oxidase

Molecular mechanism of intramolecular electron transfer in dimeric sulfite oxidase

Oxygen and nitrite reduction by heme‐deficient sulphite oxidase in a patient with mild sulphite oxidase deficiency

Selective Oxyfunctionalisation Reactions Driven by Sulfite Oxidase‐Catalysed In Situ Generation of H2O2

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Product

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Selective Oxyfunctionalisation Reactions Driven by Sulfite Oxidase‐Catalysed In Situ Generation of H₂O₂