L-amino acid oxidases: properties and molecular mechanisms of action

Лукашева, Е. В.; Efremova, A. A.; Treshalina, E. M.; Arinbasarova, A. Yu.; Medentzev, A. G.; Березов, Т. Т.

doi:10.18097/pbmc20125804372

Cited by 9 publications

(12 citation statements)

References 78 publications

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“…The sigmoidal behaviour of LO kinetics of course confirmed the allosteric behaviour of this enzyme. Indeed, as pointed out in the Introduction section, LO is a dimeric enzyme consisting of two identical subunits each one containing a FAD unit [ 2 , 4 , 5 , 6 , 7 , 8 , 9 , 10 ], thus, cooperative binding could arise; nevertheless, a pH dependence of the cooperation was never reported before and accordingly a deeper study was performed. Please note that the pH dependence on the allosteric behaviour of enzymes is not surprising, since it was already described in 1904 by Christian Bohr while studying the oxygen binding affinity of haemoglobin, a striking pH effect well-known as the Bohr effect (see for example ref.…”

Section: Resultsmentioning

confidence: 99%

“…The enzyme was firstly isolated from Trichoderma viride [ 1 , 2 ], but soon was found also in other Trichoderma species and strains [ 3 , 4 , 5 , 6 , 7 , 8 ] and characterised as well (see refs. [ 9 , 10 ] for a review). LO is an L-amino acid oxidase that is almost specific to Lys, but, depending on the enzyme source, other Lys analogues (such as L-ornithine, L-tyrosine and L-arginine) are oxidised too to some extent—no matter the analogues, it is the α-amino group of the amino acid the residue that is oxidised by the enzyme, while the terminal amino group appears to be important in the binding of amino acids to the enzyme and/or to the enzyme catalysis [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

“…LO is an L-amino acid oxidase that is almost specific to Lys, but, depending on the enzyme source, other Lys analogues (such as L-ornithine, L-tyrosine and L-arginine) are oxidised too to some extent—no matter the analogues, it is the α-amino group of the amino acid the residue that is oxidised by the enzyme, while the terminal amino group appears to be important in the binding of amino acids to the enzyme and/or to the enzyme catalysis [ 2 ]. Furthermore, LO shows a molecular weight of about 110–116 kD (depending on the source) [ 2 , 4 , 5 , 6 , 7 , 8 , 9 , 10 ] and consists of two subunits of the same molecular weight of about 55–58 kD containing one FAD per subunit [ 2 , 4 , 5 , 6 , 7 , 8 , 9 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

“…From that evidence, further biological effects, both in vitro and in vivo, were discovered (see refs. [ 9 , 10 ] for a thorough discussion). For example, LO appears to suppress DNA, RNA and protein synthesis in leukaemia, human ovary carcinoma and lymphoma tumour cells in vitro but antileukemia and antimetastatic effects in rather small effective doses have been confirmed in vivo too.…”

Section: Introductionmentioning

confidence: 99%

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Allosteric Enzyme-Based Biosensors—Kinetic Behaviours of Immobilised L-Lysine-α-Oxidase from Trichoderma viride: pH Influence and Allosteric Properties

et al. 2020

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The present study describes the kinetics of L-lysine-α-oxidase (LO) from Trichoderma viride immobilised by co-crosslinking onto the surface of a Pt electrode. The resulting amperometric biosensor was able to analyse L-lysine, thus permitting a simple but thorough study of the kinetics of the immobilised enzyme. The kinetic study evidenced that LO behaves in an allosteric fashion and that cooperativity is strongly pH-dependent. Not less important, experimental evidence shows that cooperativity is also dependent on substrate concentration at high pH and behaves as predicted by the Monod-Wyman-Changeux model for allosteric enzymes. According to this model, the existence of two different conformational states of the enzyme was postulated, which differ in Lys species landing on LO to form the enzyme–substrate complex. Considerations about the influence of the peculiar LO kinetics on biosensor operations and extracorporeal reactor devices will be discussed as well. Not less important, the present study also shows the effectiveness of using immobilised enzymes and amperometric biosensors not only for substrate analysis, but also as a convenient tool for enzyme kinetic studies.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Allosteric Enzyme-Based Biosensors—Kinetic Behaviours of Immobilised L-Lysine-α-Oxidase from Trichoderma viride: pH Influence and Allosteric Properties

et al. 2020

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“…1.4.3.2) are enzymes that catalyze the oxidative deamination of L-amino acids to their corresponding α-keto acids, with the generation of ammonia and hydrogen peroxide. They are flavoenzymes, and they show high stereospecificity toward L-isomers of amino acids (Lukasheva et al, 2011;Hossain et al, 2014). LAOs are widely distributed in nature, and they fulfill a wide spectrum of biological roles in nitrogen metabolism and in the protection against antagonists, with antimicrobial activities representing one of their main functions.…”

Section: Introductionmentioning

confidence: 99%

L-Amino Acid Oxidases From Mushrooms Show Antibacterial Activity Against the Phytopathogen Ralstonia solanacearum

et al. 2020

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Ralstonia solanaceraum is the quarantine plant pathogenic bacterium that causes bacterial wilt in over 200 host plants, which include economically important crops such as potato, tomato, tobacco, banana, and ginger. Alternative biological methods of disease control that can be used in integrated pest management are extensively studied. In search of new proteins with antibacterial activity against R. solanacearum, we identified L-amino acid oxidases (LAOs) from fruiting bodies of Amanita phalloides (ApLAO) and Infundibulicybe geotropa (CgLAO). We describe an optimized isolation procedure for their biochemical characterization, and show that they are dimeric proteins with estimated monomer molecular masses of 72 and 66 kDa, respectively, with isoelectric point of pH 6.5. They have broad substrate specificities for hydrophobic and charged amino acids, with highest K m for L-Leu, and broad pH optima at pH 5 and pH 6, respectively. An enzyme with similar properties is also characterized from the mycelia of I. geotropa (CgmycLAO). Fractionated aqueous extracts of 15 species of mushrooms show that LAO activity against L-Leu correlates with antibacterial activity. We confirm that the LAO activities mediate the antibacterial actions of ApLAO, CgLAO, and CgmycLAO. Their antibacterial activities are greater against Gram-negative versus Gram-positive bacteria, with inhibition of growth rate, prolongation of lag-phase, and decreased endpoint biomass. In Gram-positive bacteria, they mainly prolong the lag phase. These in vitro antibacterial activities of CgLAO and CgmycLAO are confirmed in vivo in tomato plants, while ApLAO has no effect on disease progression in planta. Transmission electron microscopy shows morphological changes of R. solanacearum upon LAO treatments. Finally, broad specificity of the antibacterial activities of these purified LAOs were seen for in vitro screening against 14 phytopathogenic bacteria. Therefore, these fungal LAOs show great potential as new biological phytoprotective agents and show the fruiting bodies of higher fungi to be a valuable source of antimicrobials with unique features.

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Lysine oxidase exposes a dependency on the thioredoxin antioxidant pathway in triple-negative breast cancer cells

Chepikova

Malin

Strekalova

et al. 2020

Breast Cancer Res Treat

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Purpose-Transformed cells are vulnerable to depletion of certain amino acids. Lysine oxidase (LO) catalyzes the oxidative deamination of lysine, resulting in lysine depletion and hydrogen peroxide production. Although LO has broad antitumor activity in preclinical models, the cytotoxic mechanisms of LO are poorly understood.Methods-Triple (ER/PR/HER2)-negative breast cancer (TNBC) cells were treated with control media, lysine-free media or control media supplemented with LO and examined for cell viability, caspase activation, induction of reactive oxygen species (ROS) and antioxidant signaling. To determine the role of nuclear factor erythroid 2-related factor 2 (NRF2) and thioredoxin reductatase-1 (TXNRD1) in LO-induced cell death, NRF2 and TXNRD1 were individually silenced by RNAi. Additionally, the pan-TXNRD inhibitor auranofin was used in combination with LO.Results-LO activates caspase-independent cell death that is suppressed by necroptosis and ferroptosis inhibitors, which are inactive against lysine depletion, pointing to fundamental Terms of use and reuse: academic research for non-commercial purposes, see here for full terms. https://www.springer.com/aamterms-v1

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L-amino acid oxidases: properties and molecular mechanisms of action

Cited by 9 publications

References 78 publications

Allosteric Enzyme-Based Biosensors—Kinetic Behaviours of Immobilised L-Lysine-α-Oxidase from Trichoderma viride: pH Influence and Allosteric Properties

Allosteric Enzyme-Based Biosensors—Kinetic Behaviours of Immobilised L-Lysine-α-Oxidase from Trichoderma viride: pH Influence and Allosteric Properties

L-Amino Acid Oxidases From Mushrooms Show Antibacterial Activity Against the Phytopathogen Ralstonia solanacearum

Lysine oxidase exposes a dependency on the thioredoxin antioxidant pathway in triple-negative breast cancer cells

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