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Paolo Visca - One of the best experts on this subject based on the ideXlab platform.
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peroxynitrite detoxification by ferryl Mycobacterium leprae truncated hemoglobin o
Biochemical and Biophysical Research Communications, 2009Co-Authors: Paolo Ascenzi, Paolo Visca, Elisabetta De Marinis, Chiara Ciaccio, Massimo ColettaAbstract:Abstract During infection, Mycobacterium leprae is faced with the host macrophagic environment limiting the growth of the bacilli. However, (pseudo-)enzymatic detoxification systems, including truncated hemoglobin O (Ml-trHbO), could allow this Mycobacterium to persist in vivo. Here, kinetics of peroxynitrite (ONOOH/ONOO−) detoxification by ferryl Ml-trHbO (Ml-trHbO Fe(IV) O), obtained by treatment with H2O2, is reported. Values of the second-order rate constant for peroxynitrite detoxification by Ml-trHbO Fe(IV) O (i.e., of Ml-trHbO Fe(III) formation; kon), at pH 7.2 and 22.0 °C, are 1.5 × 104 M−1 s−1, and 2.2 × 104 M−1 s−1, in the absence of and presence of physiological levels of CO2 (∼1.2 × 10−3 M), respectively. Values of kon increase on decreasing pH with a pKa value of 6.7, this suggests that ONOOH reacts preferentially with Ml-trHbO Fe(IV) O. In turn, peroxynitrite acts as an antioxidant of Ml-trHbO Fe(IV) O, which could be responsible for the oxidative damage of the Mycobacterium. As a whole, Ml-trHbO can undertake within the same cycle H2O2 and peroxynitrite detoxification.
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h2o2 and no scavenging by Mycobacterium leprae truncated hemoglobin o
Biochemical and Biophysical Research Communications, 2008Co-Authors: Paolo Ascenzi, Elisabetta De Marinis, Massimo Coletta, Paolo ViscaAbstract:Kinetics of ferric Mycobacterium leprae truncated hemoglobin O (trHbOFe(III)) oxidation by H2O2 and of trHbOFe(IV)O reduction by (.)NO and NO2- are reported. The value of the second-order rate constant for H2O2-mediated oxidation of trHbOFe(III) is 2.4 x 10(3) M(-1) s(-1). The value of the second-order rate constant for (.)NO-mediated reduction of trHbOFe(IV)O is 7.8 x 10(6) M(-1) s(-1). The value of the first-order rate constant for trHbOFe(III)ONO decay to the resting form trHbOFe(III) is 2.1 x 10(1) s(-1). The value of the second-order rate constant for NO2--mediated reduction of trHbOFe(IV)=O is 3.1 x 10(3) M(-1) s(-1). As a whole, trHbOFe(IV)O, generated upon reaction with H2O2, catalyzes (.)NO reduction to NO2-. In turn, (.)NO and NO2- act as antioxidants of trHbOFe(IV)O, which could be responsible for the oxidative damage of the Mycobacterium. Therefore, Mycobacterium leprae trHbO could be involved in both H2O2 and (.)NO scavenging, protecting from nitrosative and oxidative stress, and sustaining mycobacterial respiration.
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peroxynitrite scavenging by ferrous truncated hemoglobin glbo from Mycobacterium leprae
Biochemical and Biophysical Research Communications, 2006Co-Authors: Paolo Ascenzi, Mario Milani, Paolo ViscaAbstract:Abstract Mycobacterium leprae GlbO has been proposed to represent merging of both O 2 uptake/transport and scavenging of nitrogen reactive species. Peroxynitrite reacts with M. leprae GlbO(II)–NO leading to GlbO(III) via the GlbO(III)–NO species. The value of the second order rate constant for GlbO(III)–NO formation is >1 × 10 8 M −1 s −1 in the absence and presence of CO 2 (1.2 × 10 −3 M). The CO 2 -independent value of the first order rate constant for GlbO(III)–NO denitrosylation is (2.5 ± 0.4) × 10 1 s −1 . Furthermore, peroxynitrite reacts with GlbO(II)–O 2 leading to GlbO(III) via the GlbO(IV) O species. Values of the second order rate constant for GlbO(IV) O formation are (4.8 ± 0.5) × 10 4 and (6.3 ± 0.7) × 10 5 M −1 s −1 in the absence and presence of CO 2 (=1.2 × 10 −3 M), respectively. The value of the second order rate constant for the peroxynitrite-mediated GlbO(IV) O reduction (= (1.5 ± 0.2) × 10 4 M −1 s −1 ) is CO 2 -independent. These data argue for a role of GlbO in the defense of M. leprae against nitrosative stress.
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truncated hemoglobin glbo from Mycobacterium leprae alleviates nitric oxide toxicity
Microbial Pathogenesis, 2006Co-Authors: Giulia Fabozzi, Paolo Ascenzi, Simona Di Renzi, Paolo ViscaAbstract:As a consequence of reductive genome evolution, the obligate intracellular pathogen Mycobacterium leprae has minimized the repertoire of genes implicated in defense against reactive oxygen and nitrogen species. Genes for multiple hemoglobin types coexist in mycobacterial genomes, but M. leprae has retained only glbO, encoding a group-II truncated hemoglobin. Mycobacterium tuberculosis GlbO has been involved in oxygen transfer and respiration during hypoxia, but a role in protection from nitric oxide (NO) has not been documented yet. Here, we report that the in vitro reaction of oxygenated recombinant M. leprae GlbO with NO results in an immediate stoichiometric formation of nitrate, concomitant with heme-protein oxidation. Overexpression of GlbO alleviates the growth inhibition of Escherichia colihmp (flavohemoglobin gene) mutants in the presence of NO-donors, partly complementing the defect in Hmp synthesis. A promoter element upstream of glbO was predicted in silico, and confirmed by using a glbO::lacZ transcriptional fusion in the heterologous Mycobacterium smegmatis system. The glbO::lacZ fusion was expressed through the whole growth cycle of M. smegmatis, and moderately induced by NO. We propose that M. leprae, by retaining the unique truncated hemoglobin GlbO, may have coupled O2 delivery to the terminal oxidase with a defensive mechanism to scavenge NO from respiratory enzymes. These activities would help to sustain the obligate aerobic metabolism required for intracellular survival of leprosy bacilli.
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the truncated hemoglobin from Mycobacterium leprae
Biochemical and Biophysical Research Communications, 2002Co-Authors: Paolo Visca, Martino Bolognesi, Giulia Fabozzi, Mario Milani, Chiara Ciaccio, Massimo Coletta, Andrea Petrucca, Giampiero De Sanctis, Paolo AscenziAbstract:Truncated hemoglobins (trHb's) form a family of low molecular weight O2 binding hemoproteins distributed in eubacteria, protozoa, and plants. TrHb's branch in a distinct clade within the hemoglobin (Hb) superfamily. A unique globin gene has recently been identified from the complete genome sequence of Mycobacterium leprae that is predicted to encode a trHb (M. leprae trHbO). Sequence comparison and modelling considerations indicate that monomeric M. leprae trHbO has structural features typical of trHb's, such as 20-40 fewer residues than conventional globin chains, Gly-based sequence consensus motifs, likely assembling into a 2-on-2 alpha-helical sandwich fold, and hydrophobic residues recognized to build up the protein matrix ligand diffusion tunnel. The ferrous heme iron atom of deoxygenated M. leprae trHbO appears to be hexacoordinated, like in Arabidopsis thaliana trHbO-3 (A. thaliana trHbO-3). Accordingly, the value of the second-order rate constant for M. leprae trHbO carbonylation (7.3 x 10(3) M(-1) s(-1)) is similar to that observed for A. thaliana trHbO-3 (1.4 x 10(4) M(-1) s(-1)) and turns out to be lower than that reported for carbon monoxide binding to pentacoordinated Mycobacterium tuberculosis trHbN (6.7 x 10(6) M(-1) s(-1)). The lower reactivity of M. leprae trHbO as compared to M. tuberculosis trHbN might be related to the higher susceptibility of the leprosy bacillus to toxic nitrogen and oxygen species produced by phagocytic cells.
Paolo Ascenzi - One of the best experts on this subject based on the ideXlab platform.
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peroxynitrite detoxification by ferryl Mycobacterium leprae truncated hemoglobin o
Biochemical and Biophysical Research Communications, 2009Co-Authors: Paolo Ascenzi, Paolo Visca, Elisabetta De Marinis, Chiara Ciaccio, Massimo ColettaAbstract:Abstract During infection, Mycobacterium leprae is faced with the host macrophagic environment limiting the growth of the bacilli. However, (pseudo-)enzymatic detoxification systems, including truncated hemoglobin O (Ml-trHbO), could allow this Mycobacterium to persist in vivo. Here, kinetics of peroxynitrite (ONOOH/ONOO−) detoxification by ferryl Ml-trHbO (Ml-trHbO Fe(IV) O), obtained by treatment with H2O2, is reported. Values of the second-order rate constant for peroxynitrite detoxification by Ml-trHbO Fe(IV) O (i.e., of Ml-trHbO Fe(III) formation; kon), at pH 7.2 and 22.0 °C, are 1.5 × 104 M−1 s−1, and 2.2 × 104 M−1 s−1, in the absence of and presence of physiological levels of CO2 (∼1.2 × 10−3 M), respectively. Values of kon increase on decreasing pH with a pKa value of 6.7, this suggests that ONOOH reacts preferentially with Ml-trHbO Fe(IV) O. In turn, peroxynitrite acts as an antioxidant of Ml-trHbO Fe(IV) O, which could be responsible for the oxidative damage of the Mycobacterium. As a whole, Ml-trHbO can undertake within the same cycle H2O2 and peroxynitrite detoxification.
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h2o2 and no scavenging by Mycobacterium leprae truncated hemoglobin o
Biochemical and Biophysical Research Communications, 2008Co-Authors: Paolo Ascenzi, Elisabetta De Marinis, Massimo Coletta, Paolo ViscaAbstract:Kinetics of ferric Mycobacterium leprae truncated hemoglobin O (trHbOFe(III)) oxidation by H2O2 and of trHbOFe(IV)O reduction by (.)NO and NO2- are reported. The value of the second-order rate constant for H2O2-mediated oxidation of trHbOFe(III) is 2.4 x 10(3) M(-1) s(-1). The value of the second-order rate constant for (.)NO-mediated reduction of trHbOFe(IV)O is 7.8 x 10(6) M(-1) s(-1). The value of the first-order rate constant for trHbOFe(III)ONO decay to the resting form trHbOFe(III) is 2.1 x 10(1) s(-1). The value of the second-order rate constant for NO2--mediated reduction of trHbOFe(IV)=O is 3.1 x 10(3) M(-1) s(-1). As a whole, trHbOFe(IV)O, generated upon reaction with H2O2, catalyzes (.)NO reduction to NO2-. In turn, (.)NO and NO2- act as antioxidants of trHbOFe(IV)O, which could be responsible for the oxidative damage of the Mycobacterium. Therefore, Mycobacterium leprae trHbO could be involved in both H2O2 and (.)NO scavenging, protecting from nitrosative and oxidative stress, and sustaining mycobacterial respiration.
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peroxynitrite scavenging by ferrous truncated hemoglobin glbo from Mycobacterium leprae
Biochemical and Biophysical Research Communications, 2006Co-Authors: Paolo Ascenzi, Mario Milani, Paolo ViscaAbstract:Abstract Mycobacterium leprae GlbO has been proposed to represent merging of both O 2 uptake/transport and scavenging of nitrogen reactive species. Peroxynitrite reacts with M. leprae GlbO(II)–NO leading to GlbO(III) via the GlbO(III)–NO species. The value of the second order rate constant for GlbO(III)–NO formation is >1 × 10 8 M −1 s −1 in the absence and presence of CO 2 (1.2 × 10 −3 M). The CO 2 -independent value of the first order rate constant for GlbO(III)–NO denitrosylation is (2.5 ± 0.4) × 10 1 s −1 . Furthermore, peroxynitrite reacts with GlbO(II)–O 2 leading to GlbO(III) via the GlbO(IV) O species. Values of the second order rate constant for GlbO(IV) O formation are (4.8 ± 0.5) × 10 4 and (6.3 ± 0.7) × 10 5 M −1 s −1 in the absence and presence of CO 2 (=1.2 × 10 −3 M), respectively. The value of the second order rate constant for the peroxynitrite-mediated GlbO(IV) O reduction (= (1.5 ± 0.2) × 10 4 M −1 s −1 ) is CO 2 -independent. These data argue for a role of GlbO in the defense of M. leprae against nitrosative stress.
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truncated hemoglobin glbo from Mycobacterium leprae alleviates nitric oxide toxicity
Microbial Pathogenesis, 2006Co-Authors: Giulia Fabozzi, Paolo Ascenzi, Simona Di Renzi, Paolo ViscaAbstract:As a consequence of reductive genome evolution, the obligate intracellular pathogen Mycobacterium leprae has minimized the repertoire of genes implicated in defense against reactive oxygen and nitrogen species. Genes for multiple hemoglobin types coexist in mycobacterial genomes, but M. leprae has retained only glbO, encoding a group-II truncated hemoglobin. Mycobacterium tuberculosis GlbO has been involved in oxygen transfer and respiration during hypoxia, but a role in protection from nitric oxide (NO) has not been documented yet. Here, we report that the in vitro reaction of oxygenated recombinant M. leprae GlbO with NO results in an immediate stoichiometric formation of nitrate, concomitant with heme-protein oxidation. Overexpression of GlbO alleviates the growth inhibition of Escherichia colihmp (flavohemoglobin gene) mutants in the presence of NO-donors, partly complementing the defect in Hmp synthesis. A promoter element upstream of glbO was predicted in silico, and confirmed by using a glbO::lacZ transcriptional fusion in the heterologous Mycobacterium smegmatis system. The glbO::lacZ fusion was expressed through the whole growth cycle of M. smegmatis, and moderately induced by NO. We propose that M. leprae, by retaining the unique truncated hemoglobin GlbO, may have coupled O2 delivery to the terminal oxidase with a defensive mechanism to scavenge NO from respiratory enzymes. These activities would help to sustain the obligate aerobic metabolism required for intracellular survival of leprosy bacilli.
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the truncated hemoglobin from Mycobacterium leprae
Biochemical and Biophysical Research Communications, 2002Co-Authors: Paolo Visca, Martino Bolognesi, Giulia Fabozzi, Mario Milani, Chiara Ciaccio, Massimo Coletta, Andrea Petrucca, Giampiero De Sanctis, Paolo AscenziAbstract:Truncated hemoglobins (trHb's) form a family of low molecular weight O2 binding hemoproteins distributed in eubacteria, protozoa, and plants. TrHb's branch in a distinct clade within the hemoglobin (Hb) superfamily. A unique globin gene has recently been identified from the complete genome sequence of Mycobacterium leprae that is predicted to encode a trHb (M. leprae trHbO). Sequence comparison and modelling considerations indicate that monomeric M. leprae trHbO has structural features typical of trHb's, such as 20-40 fewer residues than conventional globin chains, Gly-based sequence consensus motifs, likely assembling into a 2-on-2 alpha-helical sandwich fold, and hydrophobic residues recognized to build up the protein matrix ligand diffusion tunnel. The ferrous heme iron atom of deoxygenated M. leprae trHbO appears to be hexacoordinated, like in Arabidopsis thaliana trHbO-3 (A. thaliana trHbO-3). Accordingly, the value of the second-order rate constant for M. leprae trHbO carbonylation (7.3 x 10(3) M(-1) s(-1)) is similar to that observed for A. thaliana trHbO-3 (1.4 x 10(4) M(-1) s(-1)) and turns out to be lower than that reported for carbon monoxide binding to pentacoordinated Mycobacterium tuberculosis trHbN (6.7 x 10(6) M(-1) s(-1)). The lower reactivity of M. leprae trHbO as compared to M. tuberculosis trHbN might be related to the higher susceptibility of the leprosy bacillus to toxic nitrogen and oxygen species produced by phagocytic cells.
Isabela Maria Bernardes Goulart - One of the best experts on this subject based on the ideXlab platform.
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oral lesion in leprosy borderline tuberculoid diagnosis based on detection of Mycobacterium leprae dna by qpcr
Acta Dermato-venereologica, 2011Co-Authors: Talita Da Silva Martinez, A A Nahas, M M N R Figueira, Adeilson Vieira Da Costa, Maria Aparecida Goncalves, Luiz Ricardo Goulart, Isabela Maria Bernardes GoulartAbstract:Oral lesions are rarely reported in paucibacillary forms of leprosy. We report here a case with an erythematous hyposensitive lesion in the palate and no skin lesions. In addition to routine tests, biopsies of the lesion in the palate and of clinically normal surrounding areas were performed and subjected to real-time PCR for detection of Mycobacterium leprae DNA. The biopsy of the oral lesion was positive for bacilli DNA, followed by positive serum anti-PGL-1 and Mitsuda test, but with negative histopathology. The patient was diagnosed with a borderline tuberculoid form. After multidrug therapy the lesion had significantly regressed and the bacilli DNA detection in the former lesion was negative. The bacilli DNA detection in an oral lesion by real-time PCR not only improved leprosy diagnosis, but also helped in the classification of clinical form, and in the establishment of the appropriate therapeutic regime.
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oral lesion in leprosy borderline tuberculoid diagnosis based on detection of Mycobacterium leprae dna by qpcr
Acta Dermato-venereologica, 2011Co-Authors: Da Silva Martinez T, A A Nahas, M M N R Figueira, Adeilson Vieira Da Costa, Maria Aparecida Goncalves, Luiz Ricardo Goulart, Isabela Maria Bernardes GoulartAbstract:Oral lesions are rarely reported in paucibacillary forms of leprosy. We report here a case with an erythematous hyposensitive lesion in the palate and no skin lesions. In addition to routine tests, biopsies of the lesion in the palate and of clinically normal surrounding areas were performed and subjected to real-time PCR for detection of Mycobacterium leprae DNA. The biopsy of the oral lesion was positive for bacilli DNA, followed by positive serum anti-PGL-1 and Mitsuda test, but with negative histopathology. The patient was diagnosed with a borderline tuberculoid form. After multidrug therapy the lesion had significantly regressed and the bacilli DNA detection in the former lesion was negative. The bacilli DNA detection in an oral lesion by real-time PCR not only improved leprosy diagnosis, but also helped in the classification of clinical form, and in the establishment of
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immunopathology of leprosy the complexity of the mechanisms of host immune response to Mycobacterium leprae
Revista Da Sociedade Brasileira De Medicina Tropical, 2002Co-Authors: Isabela Maria Bernardes Goulart, Gerson Oliveira Penna, Gabriel CunhaAbstract:Leprosy, whose etiologic agent Mycobacterium leprae, is an illness of ample clinical and immunopathological spectrum. Its clinical manifestations are correlated with distinct immunologic forms, varying from a vigorous immune response mediated by cells to M. leprae, with Th1 standard in the tuberculoid polar region, to an absence of specific cellular response to antigens of M. leprae in the lepromatous polar region, with predominance of Th2 response and exacerbation of humoral response. It is probable that different polymorphic genes determine susceptibility to M. leprae. Additional studies are necessary to clarify the complex interactions between cytokines and the role of the phenotypic diversity of cells network that contribute to the host defense. The comprehension of such mechanisms will provide new insights for the identification of agonists and/or antagonists for pro- or anti-inflammatory effects, and also will indicate possible situations for its appropriate use in immunologic and/or immunotherapeutic interventions.
A M Dhople - One of the best experts on this subject based on the ideXlab platform.
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in vitro and in vivo activity of k 130 a dihydrofolate reductase inhibitor against Mycobacterium leprae
Drug Research, 2011Co-Authors: A M DhopleAbstract:The antimicrobial effects of a new dihydrofolate reductase inhibitor, K-130 (2,4-diaminodiphenyl sulfone substituted 2,4-diamino-5-benzylpyrimidine), alone and in combination with dapsone (CAS 80-08-0) against both dapsone-sensitive and dapsone-resistant strains of Mycobacterium leprae were evaluated in vitro, in cell-free culture system, and in vivo, in mouse foot pads. The minimal inhibitory concentration of K-130 against dapsone-sensitive as well as dapsone resistant strains of M. leprae was 0.03 μg/ml, and the activity was bactericidal in both cases. However, when combined with dapsone, K-130 exhibited synergism in case of dapsone-sensitive M. leprae, while in case of dapsone-resistant M. leprae, the effect was merely additive. Similar synergistic effects were also observed in the mouse foot pad system for both types of M. leprae strains.
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in vivo activity of epiroprim a dihydrofolate reductase inhibitor singly and in combination with dapsone against Mycobacterium leprae
International Journal of Antimicrobial Agents, 2002Co-Authors: A M DhopleAbstract:The antimicrobial effects of a new dihydrofolate reductase inhibitor, epiroprim, either singly or in combination with dapsone against Mycobacterium leprae, were evaluated in vivo using a mouse footpad model. When fed to mice at concentration of 0.05% in diet, epiroprim completely inhibited the growth of both dapsone-sensitive and dapsone-resistant strains of M. leprae in the footpads of mice and the effects were bactericidal. To achieve similar effects, the concentration of dapsone in the diet had to be 0.0005 and 0.01%, respectively. When used in combination, the concentrations of the drugs in the diet could be lowered by 50-80% and still achieve bactericidal effects. The data support the earlier results on in vitro studies and suggest the use of epiroprim in the multidrug regimen in the treatment of leprosy.
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in vitro activity of epiroprim a dihydrofolate reductase inhibitor singly and in combination with brodimoprim and dapsone against Mycobacterium leprae
International Journal of Antimicrobial Agents, 1999Co-Authors: A M DhopleAbstract:The antimicrobial effects of a new dihydrofolate reductase inhibitor, epiroprim, alone and in combination with dapsone and brodimoprim against Mycobacterium leprae were evaluated in vitro in cell-free culture system. Two biochemical parameters were used to measure metabolic activity (and growth) of the organism. The minimal inhibitory activity of epiroprim against M. leprae was 10 mg/l and the action was bactericidal. When combined with dapsone, epiroprim exhibited a strong synergism; on the other hand, combination of epiroprim and brodimoprim provided only additive effects. The results suggest that epiroprim can be a component in multidrug therapy regimen in leprosy.
Massimo Coletta - One of the best experts on this subject based on the ideXlab platform.
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peroxynitrite detoxification by ferryl Mycobacterium leprae truncated hemoglobin o
Biochemical and Biophysical Research Communications, 2009Co-Authors: Paolo Ascenzi, Paolo Visca, Elisabetta De Marinis, Chiara Ciaccio, Massimo ColettaAbstract:Abstract During infection, Mycobacterium leprae is faced with the host macrophagic environment limiting the growth of the bacilli. However, (pseudo-)enzymatic detoxification systems, including truncated hemoglobin O (Ml-trHbO), could allow this Mycobacterium to persist in vivo. Here, kinetics of peroxynitrite (ONOOH/ONOO−) detoxification by ferryl Ml-trHbO (Ml-trHbO Fe(IV) O), obtained by treatment with H2O2, is reported. Values of the second-order rate constant for peroxynitrite detoxification by Ml-trHbO Fe(IV) O (i.e., of Ml-trHbO Fe(III) formation; kon), at pH 7.2 and 22.0 °C, are 1.5 × 104 M−1 s−1, and 2.2 × 104 M−1 s−1, in the absence of and presence of physiological levels of CO2 (∼1.2 × 10−3 M), respectively. Values of kon increase on decreasing pH with a pKa value of 6.7, this suggests that ONOOH reacts preferentially with Ml-trHbO Fe(IV) O. In turn, peroxynitrite acts as an antioxidant of Ml-trHbO Fe(IV) O, which could be responsible for the oxidative damage of the Mycobacterium. As a whole, Ml-trHbO can undertake within the same cycle H2O2 and peroxynitrite detoxification.
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h2o2 and no scavenging by Mycobacterium leprae truncated hemoglobin o
Biochemical and Biophysical Research Communications, 2008Co-Authors: Paolo Ascenzi, Elisabetta De Marinis, Massimo Coletta, Paolo ViscaAbstract:Kinetics of ferric Mycobacterium leprae truncated hemoglobin O (trHbOFe(III)) oxidation by H2O2 and of trHbOFe(IV)O reduction by (.)NO and NO2- are reported. The value of the second-order rate constant for H2O2-mediated oxidation of trHbOFe(III) is 2.4 x 10(3) M(-1) s(-1). The value of the second-order rate constant for (.)NO-mediated reduction of trHbOFe(IV)O is 7.8 x 10(6) M(-1) s(-1). The value of the first-order rate constant for trHbOFe(III)ONO decay to the resting form trHbOFe(III) is 2.1 x 10(1) s(-1). The value of the second-order rate constant for NO2--mediated reduction of trHbOFe(IV)=O is 3.1 x 10(3) M(-1) s(-1). As a whole, trHbOFe(IV)O, generated upon reaction with H2O2, catalyzes (.)NO reduction to NO2-. In turn, (.)NO and NO2- act as antioxidants of trHbOFe(IV)O, which could be responsible for the oxidative damage of the Mycobacterium. Therefore, Mycobacterium leprae trHbO could be involved in both H2O2 and (.)NO scavenging, protecting from nitrosative and oxidative stress, and sustaining mycobacterial respiration.
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the truncated hemoglobin from Mycobacterium leprae
Biochemical and Biophysical Research Communications, 2002Co-Authors: Paolo Visca, Martino Bolognesi, Giulia Fabozzi, Mario Milani, Chiara Ciaccio, Massimo Coletta, Andrea Petrucca, Giampiero De Sanctis, Paolo AscenziAbstract:Truncated hemoglobins (trHb's) form a family of low molecular weight O2 binding hemoproteins distributed in eubacteria, protozoa, and plants. TrHb's branch in a distinct clade within the hemoglobin (Hb) superfamily. A unique globin gene has recently been identified from the complete genome sequence of Mycobacterium leprae that is predicted to encode a trHb (M. leprae trHbO). Sequence comparison and modelling considerations indicate that monomeric M. leprae trHbO has structural features typical of trHb's, such as 20-40 fewer residues than conventional globin chains, Gly-based sequence consensus motifs, likely assembling into a 2-on-2 alpha-helical sandwich fold, and hydrophobic residues recognized to build up the protein matrix ligand diffusion tunnel. The ferrous heme iron atom of deoxygenated M. leprae trHbO appears to be hexacoordinated, like in Arabidopsis thaliana trHbO-3 (A. thaliana trHbO-3). Accordingly, the value of the second-order rate constant for M. leprae trHbO carbonylation (7.3 x 10(3) M(-1) s(-1)) is similar to that observed for A. thaliana trHbO-3 (1.4 x 10(4) M(-1) s(-1)) and turns out to be lower than that reported for carbon monoxide binding to pentacoordinated Mycobacterium tuberculosis trHbN (6.7 x 10(6) M(-1) s(-1)). The lower reactivity of M. leprae trHbO as compared to M. tuberculosis trHbN might be related to the higher susceptibility of the leprosy bacillus to toxic nitrogen and oxygen species produced by phagocytic cells.
