Mycobacterium tuberculosis, the causative agent of tuberculosis, is one of the most dreaded human pathogens that affect millions of lives worldwide (1). The inexplicable success of M. tuberculosis as a human pathogen relies on its ability to utilize a number of defense strategies to adapt its metabolism in response to a plethora of environmental challenges during the course of its pathogenic cycle (2, 3). Several of the components of its protein machinery have emerged as virulence factors with vital implications. Among these, lipoproteins play pivotal roles in several functions related to its virulence and host-pathogen interactions (4 -6). Genome analysis of mycobacteria indicated that the number of lipoproteins is much higher in the pathogenic mycobacteria in comparison with their non-pathogenic counterparts, and M. tuberculosis houses the highest number of lipoproteins.LprI is a novel lipoprotein that is exclusively present in pathogenic mycobacteria belonging to M. tuberculosis complex. The genomic location of the lprI gene is conserved among pathogenic mycobacteria where it has been identified as an operon partner of the glbN gene, which encodes truncated hemoglobin (HbN) 3 (7,8). The lprI gene is positioned adjacent to the glbN gene, separated through an intergenic distance of 58 nucleotides, and their co-transcription has been observed in Mycobacterium bovis (9), indicating that these two proteins may have functional correlation. The HbN of M. tuberculosis carries potent nitric oxide (NO) detoxification ability (8 -10) and is post-translationally modified by a glycan linkage that facilitates adherence and phagocytosis of cells during macrophage infection (11). The functional relevance of the co-occurrence of LprI with HbN in M. tuberculosis is unknown. Similar co-existence of a lipoprotein, LprG, along with Rv1410, which encodes a small molecule transporter, P55 (an operon conserved in M. tuberculosis complex), has also been observed in M. tuberculosis (12) where they function in a cooperative and synchronized manner. Because the HbN of M. tuberculosis plays a vital role in and is also involved in modulating host-pathogen interactions during intracellular infection of M. tuberculosis, it is likely that the glbN-lprI operon may also have some significant implications in the physiology of tubercle bacillus. LprI is an uncharacterized lipoprotein of M. tuberculosis complex; therefore, in the absence of any knowledge on LprI, its physiological function and implications of its co-existence with the HbN in M. tuberculosis are difficult to understand. To investigate the crucial implications of HbN in modulating the host-pathogen interactions and immune system of the host by providing aid in the better survival and sustenance of M. tuberculosis during intracellular infection, it is important to study the functionality of the LprI to understand functional implications of their co-occurrence in M. tuberculosis.In silico analysis unraveled that LprI carries a lysozyme-binding motif of the membrane-bound lysozyme in...

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Background:The HbN of Mycobacterium tuberculosis carries a potent nitric-oxide dioxygenase activity despite lacking a reductase domain. Results:The NADH-ferredoxin reductase system acts as an efficient partner for the reduction of HbN. Conclusion:The interactions of HbN with the reductase are modulated by its CD loop and the Pre-A region. Significance: The present study provides new insights into the mechanism of electron transfer during nitric oxide detoxification by HbN.

a b s t r a c tStaphylokinase (SAK) forms a 1:1 stoichiometric complex with human plasmin (Pm) and switches its substrate specificity to generate a plasminogen (Pg) activator complex. Site-directed mutagenesis of SAKHis43 and SAKTyr44 demonstrated the crucial requirement of a positively charged and an aromatic residue, respectively, at these positions for optimal functioning of SAK-Pm activator complex. Molecular modeling studies further revealed the role of these residues in making cation-pi and pipi interactions with Trp215 of Pm and thus establishing the crucial intermolecular contacts within the active site cleft of the activator complex for the cofactor activity of SAK.