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Lama, A.; Pawaria, S.; Bidon-Chanal, A.; Anand, A.; Gelpi, J.L.; Arya, S.; Marti, M.; Estrin, D.A.; Luque, F.J.; Dikshit, K.L. "Role of pre-A motif in nitric oxide scavenging by truncated hemoglobin, HbN, of Mycobacterium tuberculosis" (2009) Journal of Biological Chemistry. 284(21):14457-14468
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Abstract:

Mycobacterium tuberculosis truncated hemoglobin, HbN, is endowed with a potent nitric-oxide dioxygenase activity and has been found to relieve nitrosative stress and enhance in vivo survival of a heterologous host, Salmonella enterica Typhimurium, within the macrophages. These findings implicate involvement of HbN in the defense of M. tuberculosis against nitrosative stress. The protein carries a tunnel system composed of a short and a long tunnel branch that has been proposed to facilitate diatomic ligand migration to the heme and an unusual Pre-A motif at the N terminus, which does not contribute significantly to the structural integrity of the protein, as it protrudes out of the compact globin fold. Strikingly, deletion of Pre-A region from the M. tuberculosis HbN drastically reduces its ability to scavenge nitric oxide (NO), whereas its insertion at the N terminus of Pre-A lacking HbN of Mycobacterium smegmatis improved its nitric-oxide dioxygenase activity. Titration of the oxygenated adduct of HbN and its mutants with NO indicated that the stoichiometric oxidation of protein is severalfold slower when the Pre-A region is deleted in HbN. Molecular dynamics simulations show that the excision of Pre-A motif results in distinct changes in the protein dynamics, which cause the gate of the tunnel long branch to be trapped into a closed conformation, thus impeding migration of diatomic ligands toward the heme active site. The present study, thus, unequivocally demonstrates vital function of Pre-A region in NO scavenging and unravels its unique role by which HbN might attain its efficient NO-detoxification ability. © 2009 by The American Society for Biochemistry and Molecular Biology, Inc.

Registro:

Documento: Artículo
Título:Role of pre-A motif in nitric oxide scavenging by truncated hemoglobin, HbN, of Mycobacterium tuberculosis
Autor:Lama, A.; Pawaria, S.; Bidon-Chanal, A.; Anand, A.; Gelpi, J.L.; Arya, S.; Marti, M.; Estrin, D.A.; Luque, F.J.; Dikshit, K.L.
Filiación:Institute of Microbial Technology, Council of Scientific and Industrial Research India, Chandigarh 160036, India
Departamento de Química Inorgánica, Analítica y Química Física, Universidad de Buenos Aires, Ciudad Universitaria, Pabellón II C1428EHA, Buenos Aires, Argentina
Department of Physical Chemistry and Institute of Biomedicine, IBUB, University of Barcelona, Avda Diagonal 643, 08028 Barcelona, Spain
Palabras clave:Active site; Dioxygenase; In-vivo; M. tuberculosis; Molecular dynamics simulations; Mycobacterium smegmatis; Mycobacterium tuberculosis; Nitrosative stress; Protein dynamics; Salmonella enterica; Truncated hemoglobins; Detoxification; Dynamics; Ligands; Molecular dynamics; Nitric oxide; Porphyrins; Hemoglobin; dioxygenase; heme; hemoglobin HbN; nitric oxide; truncated hemoglobin; unclassified drug; mutant protein; nitric oxide; scavenger; truncated hemoglobin; amino terminal sequence; article; controlled study; detoxification; enzyme active site; enzyme activity; ligand binding; molecular dynamics; Mycobacterium smegmatis; Mycobacterium tuberculosis; nitric oxide scavenging; nitrosative stress; nonhuman; Pre A motif; priority journal; protein analysis; protein folding; protein function; protein interaction; protein metabolism; protein motif; protein structure; protein transport; stoichiometry; amino acid sequence; chemical structure; chemistry; circular dichroism; computer simulation; drug effect; Escherichia coli; gene deletion; metabolism; molecular genetics; oxidation reduction reaction; pliability; protein motif; protein secondary structure; structure activity relation; thermodynamics; X ray crystallography; Mycobacterium smegmatis; Mycobacterium tuberculosis; Salmonella enterica; Amino Acid Motifs; Amino Acid Sequence; Circular Dichroism; Computer Simulation; Crystallography, X-Ray; Escherichia coli; Free Radical Scavengers; Models, Molecular; Molecular Sequence Data; Mutant Proteins; Mycobacterium smegmatis; Mycobacterium tuberculosis; Nitric Oxide; Oxidation-Reduction; Pliability; Protein Structure, Secondary; Sequence Deletion; Structure-Activity Relationship; Thermodynamics; Truncated Hemoglobins
Año:2009
Volumen:284
Número:21
Página de inicio:14457
Página de fin:14468
DOI: http://dx.doi.org/10.1074/jbc.M807436200
Título revista:Journal of Biological Chemistry
Título revista abreviado:J. Biol. Chem.
ISSN:00219258
CODEN:JBCHA
CAS:dioxygenase, 37292-90-3; heme, 14875-96-8; nitric oxide, 10102-43-9; Free Radical Scavengers; Mutant Proteins; Nitric Oxide, 10102-43-9; Truncated Hemoglobins
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00219258_v284_n21_p14457_Lama

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Citas:

---------- APA ----------
Lama, A., Pawaria, S., Bidon-Chanal, A., Anand, A., Gelpi, J.L., Arya, S., Marti, M.,..., Dikshit, K.L. (2009) . Role of pre-A motif in nitric oxide scavenging by truncated hemoglobin, HbN, of Mycobacterium tuberculosis. Journal of Biological Chemistry, 284(21), 14457-14468.
http://dx.doi.org/10.1074/jbc.M807436200
---------- CHICAGO ----------
Lama, A., Pawaria, S., Bidon-Chanal, A., Anand, A., Gelpi, J.L., Arya, S., et al. "Role of pre-A motif in nitric oxide scavenging by truncated hemoglobin, HbN, of Mycobacterium tuberculosis" . Journal of Biological Chemistry 284, no. 21 (2009) : 14457-14468.
http://dx.doi.org/10.1074/jbc.M807436200
---------- MLA ----------
Lama, A., Pawaria, S., Bidon-Chanal, A., Anand, A., Gelpi, J.L., Arya, S., et al. "Role of pre-A motif in nitric oxide scavenging by truncated hemoglobin, HbN, of Mycobacterium tuberculosis" . Journal of Biological Chemistry, vol. 284, no. 21, 2009, pp. 14457-14468.
http://dx.doi.org/10.1074/jbc.M807436200
---------- VANCOUVER ----------
Lama, A., Pawaria, S., Bidon-Chanal, A., Anand, A., Gelpi, J.L., Arya, S., et al. Role of pre-A motif in nitric oxide scavenging by truncated hemoglobin, HbN, of Mycobacterium tuberculosis. J. Biol. Chem. 2009;284(21):14457-14468.
http://dx.doi.org/10.1074/jbc.M807436200