Nitric oxide (NO) is an important signaling molecule in a large variety of physiological and patholo-physiological processes. Classical L-arginine dependent NO synthases have been shown to play a key role in NO-mediated processes.
There is growing evidence that also nitrite, either derived from the oxidation of bioactive NO or from nutritional sources, is reduced back to NO to regulate processes such as blood pressure, hypoxic vasodilation, and cellular cytoprotection.
Heme proteins were found to function in nitrite-dependent NO release. We have recently identified mammalian sulfite oxidase (SOX), which is localized in the mitochondrial intermembrane space, as novel nitrite reductase.
Besides different lines of biochemical evidence, we demonstrate that in the absence of SOX, nitrite-dependent cGMP formation in fibroblast has been abolished thus confirming NO synthesis by SOX.
This project aims to understand the mechanism of NO synthesis by SOX, its in vivo function and the development of novel approached to tune nitrite-dependent NO synthesis by SOX.
Arjune S, Schwarz G, and Belaidi AA (2015). Involvement of the cys-tyr cofactor on iron binding in the active site of human cysteine dioxygenase. Amino Acids 47, 55-63.
Belaidi AA, Roper J, Arjune S, Krizowski S, Trifunovic A, and Schwarz G (2015). Oxygen reactivity of mammalian sulfite oxidase provides a concept for the treatment of sulfite oxidase deficiency. Biochem J 469, 211-221.
Chi JC, Roeper J, Schwarz G, and Fischer-Schrader K (2015). Dual binding of 14-3-3 protein regulates arabidopsis nitrate reductase activity. J Biol Inorg Chem 20, 277-286.
Dejanovic B, Djemie T, Grunewald N, Suls A, Kress V, Hetsch F, Craiu D, Zemel M, Gormley P, Lal D, Myers CT, Mefford HC, Palotie A, Helbig I, Meier JC, De Jonghe P, Weckhuysen S, and Schwarz G (2015). Simultaneous impairment of neuronal and metabolic function of mutated gephyrin in a patient with epileptic encephalopathy. EMBO Mol Med 7, 1580-94.
Imhof T, Gruenewald N, Schwarz G, Noack MJ, and Koch M (2015). Modified amelogenin is a new and versatile nanomaterial for biomedical applications. Biotechnol Bioeng 10.1002/bit.25576.
Kalimuthu P, Fischer-Schrader K, Schwarz G, and Bernhardt PV (2015). A sensitive and stable amperometric nitrate biosensor employing arabidopsis thaliana nitrate reductase. Journal of Biological Inorganic Chemistry 20, 385-393.
Reinthaler EM, Dejanovic B, Lal D, Semtner M, Merkler Y, Reinhold A, Pittrich DA, Hotzy C, Feucht M, Steinbock H, Gruber-Sedlmayr U, Ronen GM, Neophytou B, Geldner J, Haberlandt E, Muhle H, Ikram MA, van Duijn CM, Uitterlinden AG, Hofman A, Altmuller J, Kawalia A, Toliat MR, Nurnberg P, Lerche H, Nothnagel M, Thiele H, Sander T, Meier JC, Schwarz G, Neubauer BA, and Zimprich F (2015). Rare variants in gamma-aminobutyric acid type a receptor genes in rolandic epilepsy and related syndromes. Ann Neurol 77, 972-986.
Schwahn BC, Van Spronsen FJ, Belaidi AA, Bowhay S, Christodoulou J, Derks TG, Hennermann JB, Jameson E, Konig K, McGregor TL, Font-Montgomery E, Santamaria-Araujo JA, Santra S, Vaidya M, Vierzig A, Wassmer E, Weis I, Wong FY, Veldman A, and Schwarz G (2015). Efficacy and safety of cyclic pyranopterin monophosphate substitution in severe molybdenum cofactor deficiency type a: A prospective cohort study. Lancet 368, 1955-1963.
Wang J, Krizowski S, Fischer-Schrader K, Niks D, Tejero J, Sparacino-Watkins C, Wang L, Ragireddy V, Frizzell S, Kelley EE, Zhang Y, Basu P, Hille R, Schwarz G, and Gladwin MT (2015). Sulfite oxidase catalyzes single-electron transfer at molybdenum domain to reduce nitrite to nitric oxide. Antioxid Redox Signal 23, 283-294.
Winkelmann A, You X, Grunewald N, Haussler U, Krestel H, Haas CA, Schwarz G, Chen W, and Meier JC (2015). Identification of a new genomic hot spot of evolutionary diversification of protein function. PLoS One 10, e0125413.
Dejanovic B, and Schwarz G (2014). Neuronal nitric oxide synthase-dependent S-nitrosylation of gephyrin regulates gephyrin clustering at gabaergic synapses. J Neurosci 34, 7763-7768.
Dejanovic B, Lal D, Catarino CB, Arjune S, Belaidi AA, Trucks H, Vollmar C, Surges R, Kunz WS, Motameny S, Altmüller J, Kohler A, Neubauer BA, Epicure C, Nürnberg P, Noachtar S, Schwarz G, and Sander T (2014). Exonic microdeletions of the gephyrin gene impair gabaergic synaptic inhibition in patients with idiopathic generalized epilepsy. Neurobiol Dis 67, 88-96.
Dejanovic B, Semtner M, Ebert S, Lamkemeyer T, Neuser F, Luscher B, Meier JC, and Schwarz G (2014). Palmitoylation of gephyrin controls receptor clustering and plasticity of gabaergic synapses. PLoS Biol 12, e1001908.
Dreidax D, Bannert S, Henrich KO, Schroder C, Bender S, Oakes CC, Lindner S, Schulte JH, Duffy D, Schwarzl T, Saadati M, Ehemann V, Benner A, Pfister S, Fischer M, and Westermann F (2014). P19-ink4d inhibits neuroblastoma cell growth, induces differentiation and is hypermethylated and downregulated in mycn-amplified neuroblastomas. Hum Mol Genet 23, 6826-376.
Frohlich M, Dejanovic B, Kashkar H, Schwarz G, and Nussberger S (2014). S-palmitoylation represents a novel mechanism regulating the mitochondrial targeting of bax and initiation of apoptosis. Cell Death Dis 5, e1057.
Hagmann H, Bossung V, Belaidi AA, Fridman A, Karumanchi SA, Thadhani R, Schermer B, Mallmann P, Schwarz G, Benzing T, and Brinkkötter PT (2014). Low-molecular weight heparin increases circulating sflt-1 levels and enhances urinary elimination. PLoS One 9, e85258.
Havarushka N, Fischer-Schrader K, Lamkemeyer T, and Schwarz G (2014). Structural basis of thermal stability of the tungsten cofactor synthesis protein moab from pyrococcus furiosus. PLoS One 9, e86030.
Keusekotten K, Bade VN, Meyer-Teschendorf K, Sriramachandran AM, Fischer-Schrader K, Krause A, Horst C, Schwarz G, Hofmann K, Dohmen RJ, and Praefcke GJ (2014). Multivalent interactions of the sumo-interaction motifs in ring finger protein 4 determine the specificity for chains of the sumo. Biochem J 457, 207-214.
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