Blar i Department of Biomedicine på forfatter "Martinez, Aurora"
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The N-terminal sequence of tyrosine hydroxylase is a conformationally versatile motif that binds 14-3-3 proteins and membranes
Skjevik, Åge Aleksander; Mileni, Mauro; Baumann, Anne; Halskau, Øyvind; Teigen, Knut; Raymond C., Stevens; Martinez, Aurora (Peer reviewed; Journal article, 2014-01-09)Tyrosine hydroxylase (TH) catalyzes the rate-limiting step in the synthesis of catecholamine neurotransmitters, and a reduction in TH activity is associated with several neurological diseases. Human TH is regulated, among ... -
The Pah-R261Q mouse reveals oxidative stress associated with amyloid-like hepatic aggregation of mutant phenylalanine hydroxylase
Aubi Catevilla, Oscar; Prestegård, Karina Skjervheim; K C, Kunwar Jung; Shi, Tie-Jun; Ying, Ming; Grindheim, Ann Kari; Scherer, Tanja; Ulvik, Arve; McCann, Adrian; Spriet, Endy; Thöny, Beat; Martinez, Aurora (Journal article; Peer reviewed, 2021)Phenylketonuria (PKU) is caused by autosomal recessive variants in phenylalanine hydroxylase (PAH), leading to systemic accumulation of L-phenylalanine (L-Phe) that may reach neurotoxic levels. A homozygous Pah-R261Q mouse, ... -
The Peripheral Binding of 14-3-3γ to Membranes Involves Isoform-Specific Histidine Residues
Bustad, Helene J.; Skjærven, Lars; Ying, Ming; Halskau, Øyvind; Baumann, Anne; Rodriguez-Larrea, David; Costas, Miguel; Underhaug, Jarl; Sanchez-Ruiz, Jose M.; Martinez, Aurora (Peer reviewed; Journal article, 2012-11-26)Mammalian 14-3-3 protein scaffolds include seven conserved isoforms that bind numerous phosphorylated protein partners and regulate many cellular processes. Some 14-3-3-isoforms, notably γ, have elevated affinity for ... -
Personalized Medicine to Improve Treatment of Dopa-Responsive Dystonia—A Focus on Tyrosine Hydroxylase Deficiency
Nygaard, Gyrid; Szigetvari, Peter D.; Grindheim, Ann Kari; Ruoff, Peter; Martinez, Aurora; Haavik, Jan; Kleppe, Rune; Flydal, Marte I. (Journal article; Peer reviewed, 2021)Dopa-responsive dystonia (DRD) is a rare movement disorder associated with defective dopamine synthesis. This impairment may be due to the fact of a deficiency in GTP cyclohydrolase I (GTPCHI, GCH1 gene), sepiapterin ... -
A Pharmacological Chaperone Therapy for Acute Intermittent Porphyria
Bustad, Helene J.; Toska, Karen; Schmitt, Caroline; Vorland, Marta; Skjærven, Lars; Kallio, Juha Pekka; Simonin, Sylvie; Lettéron, Philippe; Underhaug, Jarl; Sandberg, Sverre; Martinez, Aurora (Peer reviewed; Journal article, 2019-12-03)Mutations in hydroxymethylbilane synthase (HMBS) cause acute intermittent porphyria (AIP), an autosomal dominant disease where typically only one HMBS allele is mutated. In AIP, the accumulation of porphyrin precursors ... -
Phenylalanine Hydroxylase from Legionella pneumophila Is a Thermostable Enzyme with a Major Functional Role in Pyomelanin Synthesis
Flydal, Marte Innselset; Chatfield, Christa H.; Zheng, Huaixin; Gunderson, Felizza F.; Aubi, Oscar; Cianciotto, Nicholas P.; Martinez, Aurora (Peer reviewed; Journal article, 2012-09-26)Background: Legionella pneumophila is a pathogenic bacterium that can cause Legionnaires’ disease and other non-pneumonic infections in humans. This bacterium produces a pyomelanin pigment, a potential virulence factor ... -
Phosphorylation at serine 31 targets tyrosine hydroxylase tovesicles for transport along microtubules
Jorge Finnigan, Ana; Kleppe, Rune; K C, Kunwar Jung; Ying, Ming; Marie, Michael Bruno Eric; Rios Mondragon, Ivan; Salvatore, Michael F; Saraste, Jaakko; Martinez, Aurora (Peer reviewed; Journal article, 2017)Tyrosine hydroxylase (TH) catalyzes the conversion of L-tyrosine into L-DOPA, which is the rate-limiting step in the synthesis of catecholamines, such as dopamine, in dopaminergergic neurons. Low dopamine levels and death ... -
Potassium channels in behavioral brain disorders. Molecular mechanisms and therapeutic potential: A narrative review
Alam, Kazi Asraful; Svalastoga, Pernille; Martinez, Aurora; Glennon, Jeffrey Colm; Haavik, Jan (Journal article; Peer reviewed, 2023)Potassium channels (K+-channels) selectively control the passive flow of potassium ions across biological membranes and thereby also regulate membrane excitability. Genetic variants affecting many of the human K+-channels ... -
The Regulatory Subunit of PKA-I Remains Partially Structured and Undergoes b-Aggregation upon Thermal Denaturation
Dao, Khanh K.; Pey, Angel; Gjerde, Anja Underhaug; Teigen, Knut; Byeon, In-Ja L.; Døskeland, Stein Ove; Gronenborn, Angela M.; Martinez, Aurora (Peer reviewed; Journal article, 2011-03-04)Background: The regulatory subunit (R) of cAMP-dependent protein kinase (PKA) is a modular flexible protein that responds with large conformational changes to the binding of the effector cAMP. Considering its highly dynamic ... -
Relevance of Electrostatics for the Interaction of Tyrosine Hydroxylase with Porous Silicon Nanoparticles
Bezem, Maria Teresa; Johannessen, Fredrik Gullaksen; Kråkenes, Trond-André; Sailor, Michael J.; Martinez, Aurora (Journal article; Peer reviewed, 2021)Tyrosine hydroxylase (TH) is the enzyme catalyzing the rate-limiting step in the synthesis of dopamine in the brain. Developing enzyme replacement therapies using TH could therefore be beneficial to patient groups with ... -
Stable preparations of tyrosine hydroxylase provide the solution structure of the full-length enzyme
Bezem, Maria Teresa; Baumann, Anne; Skjærven, Lars; Meyer, Romain; Kursula, Petri; Martinez, Aurora; Flydal, Marte Innselset (Peer reviewed; Journal article, 2016-07-27)Tyrosine hydroxylase (TH) catalyzes the rate-limiting step in the biosynthesis of catecholamine neurotransmitters. TH is a highly complex enzyme at mechanistic, structural, and regulatory levels, and the preparation of ... -
Structural and thermodynamic insight into phenylalanine hydroxylase from the human pathogen Legionella pneumophila
Leiros, Hanna-Kirsti S.; Flydal, Marte Innselset; Martinez, Aurora (Peer reviewed; Journal article, 2013-08-19)Phenylalanine hydroxylase from Legionella pneumophila (lpPAH) has a major functional role in the synthesis of the pigment pyomelanin, which is a potential virulence factor. We present here the crystal structure of lpPAH, ... -
Structural mechanism for tyrosine hydroxylase inhibition by dopamine and reactivation by Ser40 phosphorylation
Bueno-Carrasco, María Teresa; Cuellar, Jorge; Flydal, Marte Innselset; Santiago, Cesar; Kråkenes, Trond-André; Kleppe, Rune; Jose R, Lopez-Blanco; Marcilla, Miguel; Teigen, Knut; Alvira, Sara; Chacón, Pablo; Martinez, Aurora; Valpuesta, José M (Journal article; Peer reviewed, 2022)Tyrosine hydroxylase (TH) catalyzes the rate-limiting step in the biosynthesis of dopamine (DA) and other catecholamines, and its dysfunction leads to DA deficiency and parkinsonisms. Inhibition by catecholamines and ... -
Tyrosine and tryptophan hydroxylases as therapeutic targets in human disease
Waløen, Kai; Kleppe, Rune; Martinez, Aurora; Haavik, Jan (Peer reviewed; Journal article, 2017)Introduction: The ancient and ubiquitous monoamine signalling molecules serotonin, dopamine, norepinephrine, and epinephrine are involved in multiple physiological functions. The aromatic amino acid hydroxylases tyrosine ...