Publications

• Structural bases for inhibitor binding and catalysis in polyamine oxidase.

  Binda C., Angelini R., Federico R., Ascenzi P., Mattevi A.

  Polyamine oxidase (PAO) carries out the FAD-dependent oxidation of the secondary amino groups of spermidine and spermine, a key reaction in the polyamine catabolism. The active site of PAO consists of a 30 A long U-shaped catalytic tunnel, whose innermost part is located in front of the flavin rin ... >> More

  Polyamine oxidase (PAO) carries out the FAD-dependent oxidation of the secondary amino groups of spermidine and spermine, a key reaction in the polyamine catabolism. The active site of PAO consists of a 30 A long U-shaped catalytic tunnel, whose innermost part is located in front of the flavin ring. To provide insight into the PAO substrate specificity and amine oxidation mechanism, we have investigated the crystal structure of maize PAO in the reduced state and in complex with three different inhibitors, guazatine, 1,8-diaminooctane, and N(1)-ethyl-N(11)-[(cycloheptyl)methyl]-4,8-diazaundecane (CHENSpm). In the reduced state, the conformation of the isoalloxazine ring and the surrounding residues is identical to that of the oxidized enzyme. Only Lys300 moves away from the flavin to compensate for the change in cofactor protonation occurring upon reduction. The structure of the PAO.inhibitor complexes reveals an exact match between the inhibitors and the PAO catalytic tunnel. Inhibitor binding does not involve any protein conformational change. Such lock-and-key binding occurs also in the complex with CHENSpm, which forms a covalent adduct with the flavin N5 atom. Comparison of the enzyme complexes hints at an "out-of-register" mechanism of inhibition, in which the inhibitor secondary amino groups are not properly aligned with respect to the flavin to allow oxidation. Except for the Glu62-Glu170 pair, no negatively charged residues are involved in the recognition of substrate and inhibitor amino groups, which is in contrast to other polyamine binding proteins. This feature may be exploited in the design of drugs specifically targeting PAO. << Less

  Biochemistry 40:2766-2776(2001) [PubMed] [EuropePMC]

  This publication is cited by 1 other entry.

• Functions of amine oxidases in plant development and defence.

  Cona A., Rea G., Angelini R., Federico R., Tavladoraki P.

  Copper amine oxidases and flavin-containing amine oxidases catalyse the oxidative de-amination of polyamines, which are ubiquitous compounds essential for cell growth and proliferation. Far from being only a means of degrading cellular polyamines and, thus, contributing to polyamine homeostasis, a ... >> More

  Copper amine oxidases and flavin-containing amine oxidases catalyse the oxidative de-amination of polyamines, which are ubiquitous compounds essential for cell growth and proliferation. Far from being only a means of degrading cellular polyamines and, thus, contributing to polyamine homeostasis, amine oxidases participate in important physiological processes through their reaction products. In plants, the production of hydrogen peroxide (H(2)O(2)) deriving from polyamine oxidation has been correlated with cell wall maturation and lignification during development as well as with wound-healing and cell wall reinforcement during pathogen invasion. As a signal molecule, H(2)O(2) derived from polyamine oxidation mediates cell death, the hypersensitive response and the expression of defence genes. Furthermore, aminoaldehydes and 1,3-diaminopropane from polyamine oxidation are involved in secondary metabolite synthesis and abiotic stress tolerance. << Less

  Trends Plant Sci 11:80-88(2006) [PubMed] [EuropePMC]

  This publication is cited by 1 other entry.

• FAD-containing polyamine oxidases: a timely challenge for researchers in biochemistry and physiology of plants.

  Sebela M., Radova A., Angelini R., Tavladoraki P., Frebort, Pec P.

  Recent investigations on plant polyamine oxidase (PAO) are reviewed. The enzyme belongs to a new class of flavoenzymes with similar structural features including, among others, monoamine oxidase. Plant PAOs catalyse the oxidation of the polyamine substrates spermidine and spermine. The reaction pr ... >> More

  Recent investigations on plant polyamine oxidase (PAO) are reviewed. The enzyme belongs to a new class of flavoenzymes with similar structural features including, among others, monoamine oxidase. Plant PAOs catalyse the oxidation of the polyamine substrates spermidine and spermine. The reaction products are propane-1,3-diamine and 1-pyrroline or 1-(3-aminopropyl)pyrrolinium, respectively, along with hydrogen peroxide. Plant PAOs are predominantly localised in the cell wall. Purification procedures and molecular properties of several plant PAOs are compared. A special attention is being paid to the recently solved crystal structure of the maize enzyme and its implications for the substrate binding and catalytic mechanism. Substrate specificity and inhibitors of plant PAOs are also described. The potential roles for PAO-generated H(2)O(2) in lignin biosynthesis and cell wall cross-linking reactions, which may regulate growth and contribute to cell defence, are discussed. << Less

  Plant Sci 160:197-207(2001) [PubMed] [EuropePMC]

  This publication is cited by 2 other entries.