Activity‐Based Probes for Studying the Activity of Flavin‐Dependent Oxidases and for the Protein Target Profiling of Monoamine Oxidase Inhibitors

Krysiak, Joanna; Kreuzer, Johannes; Macheroux, Peter; Hermetter, Albin; Sieber, Stephan A.; Breinbauer, Rolf

doi:10.1002/anie.201201955

Cited by 65 publications

(40 citation statements)

References 77 publications

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“…Type-specificity was confirmed, but the in situ labeling was not correlated with enzymatic activity and protein levels. In addition, both isolated and membrane-bound MAO, as well as enzyme localized in mitochondria or cytoplasm, exhibited varying affinities for ligands, underlining the difficulty involved in quantitative determination of in vivo MAO inhibitor binding (Krysiak et al 2012).…”

Section: Parkinmentioning

confidence: 97%

Modulation of monoamine oxidase (MAO) expression in neuropsychiatric disorders: genetic and environmental factors involved in type A MAO expression

2015

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Monoamine oxidase types A and B (MAO-A, MAO-B) regulate the levels of monoamine neurotransmitters in the brain, and their dysfunction may be involved in the pathogenesis and influence the clinical phenotypes of neuropsychiatric disorders. Reversible MAO-A inhibitors, such as moclobemide and befloxatone, are currently employed in the treatment of emotional disorders by inhibiting the enzymatic degradation of dopamine, serotonin and norepinephrine in the central nervous system (CNS). It has been suggested that the irreversible MAO-B inhibitors selegiline and rasagiline exert a neuroprotective effect in Parkinson's and Alzheimer's diseases. This effect, however, is not related to their inhibition of MAO activity; in animal and cellular models, selegiline and rasagiline protect neuronal cells through their anti-apoptotic activity and induction of pro-survival genes. There is increasing evidence that MAO-A activity, but not that of MAO-B, is implicated in the pathophysiology of neurodegenerative disorders, but also in gene induction by MAO-B inhibitors; on the other hand, selegiline and rasagiline increase MAO-A mRNA, protein, and enzyme activity levels. Taken together, these results suggest that each MAO subtype exerts effects that modulate the expression and activity of the other isoenzyme. The roles of MAO-A and -B in the CNS should therefore be re-evaluated with respect to the "type-specificity" of their inhibitors, which may not be unconditional during chronic treatment. Mao-a expression, in particular, may be implicated in pathogenesis and phenotypes in neuropsychiatric disorders. MAO-A expression is modified by mao polymorphisms affecting its transcriptional efficiency, as well as by mutations and polymorphism of parkin, Sirt1, FOXO, microRNA, presenilin-1, and other regulatory proteins. In addition, childhood maltreatment has been shown to have an impact upon adolescent social behavior in children with mao-a polymorphisms of low transcriptional activity. Low MAO-A activity may increase the levels of serotonin and norepinephrine, resulting in disturbed neurotransmitter system development and behavior. This review discusses genetic and environmental factors involved in the regulation of MAO-A expression, in the contexts of neuropsychiatric function and of the regulation of neuronal survival and death.

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Section: Parkinmentioning

confidence: 97%

Modulation of monoamine oxidase (MAO) expression in neuropsychiatric disorders: genetic and environmental factors involved in type A MAO expression

2015

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“…Other "label-free", surrogate group-bearing probes reported so far include probes for histone deacetylases (HDACs, 20, 21), [44] methionine aminopeptidase (22), [45] transglutaminase (23), [46] protein phosphatase methylesterase (24), [47] fatty acid amide hydrolase (FAAH) (25), [48] the 14-3-3 family of phosphorbinding protein (26), [49] fatty acid associate proteins (27,28), [50] flavin-dependent oxidases (29), [51] and protein arginine deiminase (30). [52] Although the aforementioned directed "label-free" probes are widely employed for targeting proteins with known inhibitors, many enzyme classes lack such cognate inhibitors that could inspire probe development.…”

Section: Activity-and Affinity-based Probes For Proteomic Profilingmentioning

confidence: 99%

Activity‐Based Protein Profiling: Recent Advances in Probe Development and Applications

Yang

2015

ChemBioChem

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The completion of the human genome sequencing project has provided a wealth of new information regarding the genomic blueprint of the cell. Although, to date, there are roughly 20,000 genes in the human genome, the functions of only a handful of proteins are clear. The major challenge lies in translating genomic information into an understanding of their cellular functions. The recently developed activity-based protein profiling (ABPP) is an unconventional approach that is complementary for gene expression analysis and an ideal utensil in decoding this overflow of genomic information. This approach makes use of synthetic small molecules that covalently modify a set of related proteins and subsequently facilitates identification of the target protein, enabling rapid biochemical analysis and inhibitor discovery. This tutorial review introduces recent advances in the field of ABPP and its applications.

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“…Many other ABPs have been generated and validated in complex proteomes, including but not limited to: 1) 2-oxoglutarate-dependent oxygenase probes that employ a hydroxyquinoline template coupled to a photoactivatable crosslinking group and biotin handle (Rotili et al, 2011), 2) S-adenosylmethionine (SAM)-dependent methyltransferase probes that consist of S-adenosylhomocysteine analogs with amino linkers attached to scaffolds containing photocrosslinkers and a biotin handle (Dalhoff et al, 2010), 3) a suite of bioorthogonal cytochrome P450 ABPs against a wide cross-section of human P450s (Wright and Cravatt, 2007; Wright et al, 2009), and 4) pargyline and deprenyl-based bioorthogonal ABPs for monoamine oxidase (Krysiak et al, 2012). …”

Section: Chemoproteomic Approaches To Assess the Functional State Of mentioning

confidence: 99%

Exploring Metabolic Pathways and Regulation through Functional Chemoproteomic and Metabolomic Platforms

Medina-Cleghorn¹,

Nomura²

2014

Chemistry & Biology

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Genome sequencing efforts have revealed a strikingly large number of uncharacterized genes, including poorly or uncharacterized metabolic enzymes, metabolites, and metabolic networks that operate in normal physiology, and also those enzymes and pathways that may be rewired under pathological conditions. Though deciphering the functions of the uncharacterized metabolic genome is a challenging prospect, it also presents an opportunity for identifying novel metabolic nodes that may be important in disease therapy. In this review, we will discuss the chemoproteomic and metabolomic platforms employed in identifying, characterizing, and targeting nodal metabolic pathways important in physiology and disease, describing an integrated workflow for functional mapping of metabolic enzymes.

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Activity‐Based Probes for Studying the Activity of Flavin‐Dependent Oxidases and for the Protein Target Profiling of Monoamine Oxidase Inhibitors

Cited by 65 publications

References 77 publications

Modulation of monoamine oxidase (MAO) expression in neuropsychiatric disorders: genetic and environmental factors involved in type A MAO expression

Modulation of monoamine oxidase (MAO) expression in neuropsychiatric disorders: genetic and environmental factors involved in type A MAO expression

Activity‐Based Protein Profiling: Recent Advances in Probe Development and Applications

Exploring Metabolic Pathways and Regulation through Functional Chemoproteomic and Metabolomic Platforms

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