title: Crystal structure of the toxin Msmeg_6760, the structural homolog of Mycobacterium tuberculosis Rv2035, a novel type II toxin involved in the hypoxic response.
abstract: The structure of Msmeg_6760, a protein of unknown function, has been determined. Biochemical and bioinformatics analyses determined that Msmeg_6760 interacts with a protein encoded in the same operon, Msmeg_6762, and predicted that the operon is a toxin-antitoxin (TA) system. Structural comparison of Msmeg_6760 with proteins of known function suggests that Msmeg_6760 binds a hydrophobic ligand in a buried cavity lined by large hydrophobic residues. Access to this cavity could be controlled by a gate-latch mechanism. The function of the Msmeg_6760 toxin is unknown, but structure-based predictions revealed that Msmeg_6760 and Msmeg_6762 are homologous to Rv2034 and Rv2035, a predicted novel TA system involved in Mycobacterium tuberculosis latency during macrophage infection. The Msmeg_6760 toxin fold has not been previously described for bacterial toxins and its unique structural features suggest that toxin activation is likely to be mediated by a novel mechanism.
authors.affiliation: UCLA-DOE Institute and Departments of Biological Chemistry and Chemistry and Biochemistry, University of California, Los Angeles, CA 90095-1570, USA.
authors.forename: R Alexandra
authors.initials: RA
authors.lastname: Bajaj
authors.affiliation: UCLA-DOE Institute and Departments of Biological Chemistry and Chemistry and Biochemistry, University of California, Los Angeles, CA 90095-1570, USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Arbing
authors.affiliation: UCLA-DOE Institute and Departments of Biological Chemistry and Chemistry and Biochemistry, University of California, Los Angeles, CA 90095-1570, USA.
authors.forename: Annie
authors.initials: A
authors.lastname: Shin
authors.affiliation: UCLA-DOE Institute and Departments of Biological Chemistry and Chemistry and Biochemistry, University of California, Los Angeles, CA 90095-1570, USA.
authors.forename: Duilio
authors.initials: D
authors.lastname: Cascio
authors.affiliation: UCLA-DOE Institute and Departments of Biological Chemistry and Chemistry and Biochemistry, University of California, Los Angeles, CA 90095-1570, USA.
authors.forename: Linda
authors.initials: L
authors.lastname: Miallau
mesh_terms: D000595:Amino Acid Sequence; D000942:Antigens, Bacterial; D000992:Antitoxins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D001426:Bacterial Proteins; D001427:Bacterial Toxins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites; D003001:Cloning, Molecular; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D015964:Gene Expression Regulation, Bacterial; D008958:Models, Molecular; D020102:Mycobacterium smegmatis / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D009169:Mycobacterium tuberculosis / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D009876:Operon; D010957:Plasmids / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D000072756:Protein Conformation, alpha-Helical; D000072757:Protein Conformation, beta-Strand; D054730:Protein Interaction Domains and Motifs; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins; D000075704:Toxin-Antitoxin Systems / Q000235:genetics*
chemical_list: D000942:Antigens, Bacterial; D000992:Antitoxins; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D011994:Recombinant Proteins; D012097:Repressor Proteins; C000593589:Rv2034 protein, Mycobacterium tuberculosis
keywords: Mycobacterium smegmatis; Mycobacterium tuberculosis; X-ray crystallography; bacterial latency; macrophage infection; novel folds; protein structure; toxin–antitoxin complexes