Overexpression of a Maize Sulfite Oxidase Gene in Tobacco Enhances Tolerance to Sulfite Stress via Sulfite Oxidation and CAT-Mediated H2O2 Scavenging

AbstractSulfite oxidase (SO) is encoded by the nuclear SUOX gene and catalyzes the final step in cysteine catabolism thereby oxidizing sulfite to sulfate. Oxidation of sulfite is dependent on two cofactors within SO, a heme and the molybdenum cofactor (Moco), the latter forming the catalytic site of sulfite oxidation. SO localizes to the intermembrane space of mitochondria where both—pre-SO processing and cofactor insertion—are essential steps during SO maturation. Isolated SO deficiency (iSOD) is a rare inborn error of metabolism caused by mutations in the SUOX gene that lead to non-functional SO. ISOD is characterized by rapidly progressive neurodegeneration and death in early infancy. We diagnosed an iSOD patient with homozygous mutation of SUOX at c.1084G>A replacing Gly362 to serine. To understand the mechanism of disease, we expressed patient-derived G362S SO in Escherichia coli and surprisingly found full catalytic activity, while in patient fibroblasts no SO activity was detected, suggesting differences between bacterial and human expression. Moco reconstitution of apo-G362S SO was found to be approximately 90-fold reduced in comparison to apo-WT SO in vitro. In line, levels of SO-bound Moco in cells overexpressing G362S SO were significantly reduced compared to cells expressing WT SO providing evidence for compromised maturation of G362S SO in cellulo. Addition of molybdate to culture medium partially rescued impaired Moco binding of G362S SO and restored SO activity in patient fibroblasts. Thus, this study demonstrates the importance of the orchestrated maturation of SO and provides a first case of Moco-responsive iSOD.

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Structure-Based Alteration of Substrate Specificity and Catalytic Activity of Sulfite Oxidase from Sulfite Oxidation to Nitrate Reduction

Biochemistry ◽

10.1021/bi201206v ◽

2012 ◽

Vol 51 (6) ◽

pp. 1134-1147 ◽

Cited By ~ 11

Author(s):

James A. Qiu ◽

Heather L. Wilson ◽

K. V. Rajagopalan

Keyword(s):

Catalytic Activity ◽

Substrate Specificity ◽

Nitrate Reduction ◽

Sulfite Oxidase ◽

Sulfite Oxidation

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Neurologic Injury in Isolated Sulfite Oxidase Deficiency

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/s0317167100016243 ◽

2014 ◽

Vol 41 (1) ◽

pp. 42-48 ◽

Cited By ~ 11

Author(s):

Thomas M. Bosley ◽

Ibrahim A. Alorainy ◽

Darren T. Oystreck ◽

Ali M. Hellani ◽

Mohammed Z. Seidahmed ◽

...

Keyword(s):

Sulfite Oxidase ◽

Neurologic Injury ◽

Oxidase Deficiency ◽

Genetic Studies ◽

Oxidase Gene ◽

Nuclear Families ◽

Sulfite Oxidase Deficiency ◽

Neurologic Development ◽

Clinical Records ◽

The Brain

Background:We review clinical, neuroimaging, and genetic information on six individuals with isolated sulfite oxidase deficiency (ISOD).Methods:All patients were examined, and clinical records, biochemistry, neuroimaging, and sulfite oxidase gene (SUOX) sequencing were reviewed.Results:Data was available on six individuals from four nuclear families affected by ISOD. Each individual began to seize within the first week of life. neurologic development was arrested at brainstem reflexes, and severe microcephaly developed rapidly. neuroimaging within days of birth revealed hypoplasia of the cerebellum and corpus callosum and damage to the supratentorial brain looking like severe hypoxic-ischemic injury that evolved into cystic hemispheric white matter changes. Affected individuals all had elevated urinary S-sulfocysteine and normal urinary xanthine and hypoxanthine levels diagnostic of ISOD. Genetic studies confirmed SUOX mutations in four patients.Conclusions:ISOD impairs systemic sulfite metabolism, and yet this genetic disease affects only the brain with damage that is commonly confused with the clinical and radiologic features of severe hypoxic-ischemic encephalopathy.

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

Nitric Oxide ◽

10.1016/j.niox.2019.04.004 ◽

2019 ◽

Vol 89 ◽

pp. 22-31 ◽

Cited By ~ 2

Author(s):

Alexander T. Kaczmarek ◽

Marc J.F. Strampraad ◽

Peter-Leon Hagedoorn ◽

Guenter Schwarz

Keyword(s):

Sulfite Oxidase ◽

Nitrite Reduction ◽

Reciprocal Regulation ◽

Sulfite Oxidation

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Stable clinical course in three siblings with late-onset isolated sulfite oxidase deficiency: a case series and literature review

BMC Pediatrics ◽

10.1186/s12887-019-1889-5 ◽

2019 ◽

Vol 19 (1) ◽

Author(s):

Maoqiang Tian ◽

Yi Qu ◽

Lingyi Huang ◽

Xiaojuan Su ◽

Shiping Li ◽

...

Keyword(s):

Spontaneous Recovery ◽

Clinical Course ◽

Late Onset ◽

Sulfite Oxidase ◽

Plasma Homocysteine ◽

Dietary Therapy ◽

Compound Heterozygous ◽

Oxidase Deficiency ◽

Oxidase Gene ◽

Sulfite Oxidase Deficiency

Abstract Background Isolated sulfite oxidase deficiency (ISOD) is an autosomal recessive disorder caused by a deficiency of sulfite oxidase, which is encoded by the sulfite oxidase gene (SUOX). Clinically, the disorder is classified as one of two forms: the late-onset mild form or the classic early-onset form. The latter is life-threatening and always leads to death during early childhood. Mild ISOD cases are rare and may benefit from dietary therapy. To date, no cases of ISOD have been reported to recover spontaneously. Here, we present three mild ISOD cases in one family, each with a stable clinical course and spontaneous recovery. Case presentation All three siblings had two novel compound heterozygous mutations in the SUOX gene (NM_000456; c.1096C > T [p.R366C] and c.1376G > A [p.R459Q]). The siblings included two males and one female with late ages of onset (12–16 months) and presented with specific neuroimaging abnormalities limited to the bilateral globus pallidus and substantia nigra. The three patients had decreased plasma homocysteine levels. They exhibited a monophasic clinical course continuing up to 8.5 years even without dietary therapy. Conclusion This is the first report of mild ISOD cases with a stable clinical course and spontaneous recovery without dietary therapy. Our study provides an expansion for the clinical spectrum of ISOD. Furthermore, we highlight the importance of including ISOD in the differential diagnosis for patients presenting with late-onset symptoms, bilaterally symmetric regions of abnormal intensities in the basal ganglia, and decreased plasma homocysteine levels.

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Identification and Biochemical Characterization ofArabidopsis thalianaSulfite Oxidase

Journal of Biological Chemistry ◽

10.1074/jbc.m108078200 ◽

2001 ◽

Vol 276 (50) ◽

pp. 46989-46994 ◽

Cited By ~ 119

Author(s):

Thomas Eilers ◽

Günter Schwarz ◽

Henner Brinkmann ◽

Christina Witt ◽

Tim Richter ◽

...

Keyword(s):

Biochemical Characterization ◽

Sulfite Oxidase ◽

Molybdenum Cofactor ◽

Active Centers ◽

Oxidase Gene ◽

Cell Extracts ◽

Redox Active ◽

Wide Range ◽

Heme Domain ◽

Molybdenum Enzyme

In mammals and birds, sulfite oxidase (SO) is a homodimeric molybdenum enzyme consisting of an N-terminal heme domain and a C-terminal molybdenum domain (EC1.8.3.1). In plants, the existence of SO has not yet been demonstrated, while sulfite reductase as part of sulfur assimilation is well characterized. Here we report the cloning of a plant sulfite oxidase gene fromArabidopsis thalianaand the biochemical characterization of the encoded protein (At-SO). At-SO is a molybdenum enzyme with molybdopterin as an organic component of the molybdenum cofactor. In contrast to homologous animal enzymes, At-SO lacks the heme domain, which is evident both from the amino acid sequence and from its enzymological and spectral properties. Thus, among eukaryotes, At-SO is the only molybdenum enzyme yet described possessing no redox-active centers other than the molybdenum. UV-visible and EPR spectra as well as apparentKmvalues are presented and compared with the hepatic enzyme. Subcellular analysis of crude cell extracts showed that SO was mostly found in the peroxisomal fraction. In molybdenum cofactor mutants, the activity of SO was strongly reduced. Using antibodies directed against At-SO, we show that a cross-reacting protein of similar size occurs in a wide range of plant species, including both herbacious and woody plants.

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