<?xml version="1.0" encoding="UTF-8"?><xml><records><record><source-app name="Biblio" version="6.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Lama,A.</style></author><author><style face="normal" font="default" size="100%">Pawaria,S.</style></author><author><style face="normal" font="default" size="100%">A. Bidon-Chanal</style></author><author><style face="normal" font="default" size="100%">Anand,A.</style></author><author><style face="normal" font="default" size="100%">Gelpi,J. L.</style></author><author><style face="normal" font="default" size="100%">Arya,S.</style></author><author><style face="normal" font="default" size="100%">Marti,M.</style></author><author><style face="normal" font="default" size="100%">D. A. Estrin</style></author><author><style face="normal" font="default" size="100%">F. J. Luque</style></author><author><style face="normal" font="default" size="100%">Dikshit,K. L.</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Role of Pre-A motif in nitric oxide scavenging by truncated hemoglobin, HbN, of Mycobacterium tuberculosis</style></title><secondary-title><style face="normal" font="default" size="100%">The Journal of biological chemistry</style></secondary-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Amino Acid Motifs; Amino Acid Sequence; Circular Dichroism; Computer Simulation; Crystallography</style></keyword><keyword><style  face="normal" font="default" size="100%">Molecular; Molecular Sequence Data; Mutant Proteins/chemistry/metabolism; Mycobacterium smegmatis/drug effects/metabolism; Mycobacterium tuberculosis/drug effects/metabolism; Nitric Oxide/metabolism/toxicity; Oxidation-Reduction/drug effects; Pliability/d</style></keyword><keyword><style  face="normal" font="default" size="100%">Secondary; Sequence Deletion/drug effects; Structure-Activity Relationship; Thermodynamics; Truncated Hemoglobins/chemistry/metabolism</style></keyword><keyword><style  face="normal" font="default" size="100%">X-Ray; Escherichia coli/drug effects; Free Radical Scavengers/metabolism; Models</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2009</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2009/05/22/</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">284</style></volume><pages><style face="normal" font="default" size="100%">14457 - 14468</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">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.</style></abstract><issue><style face="normal" font="default" size="100%">21</style></issue></record></records></xml>