title: Comparative structure-function analysis of cytolethal distending toxins.
abstract: Cytolethal distending toxins (CDTs) constitute a family of bacterial proteins that enter eukaryotic cells with genotoxic activity leading to cell cycle arrest and apoptosis. CDTs are widespread, having been found in a variety of Gram-negative pathogens with a broad tissue tropism. The recently determined crystal structure of the Haemophilus ducreyi CDT provides a powerful starting point for analysis of the structure and function in this toxin family. In this study, we apply comparative modeling and structural analysis to extend the experimental structural information to multiple CDT toxins from a diverse species. Analysis of structurally and functionally important residues in the active subunit, CdtB, and putative cell delivery elements, CdtA and CdtC, begins to establish the fundamental, mechanistic elements of this unique holotoxin. The results reveal that key structural features with important functional consequences are highly conserved across different CDTs, providing a blueprint for directed examination of functional hypotheses in a variety of pathogenic contexts.
authors.affiliation: Laboratory of Structural Microbiology, The Rockefeller University, New York, New York 10021, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Hu
authors.forename: Dragana
authors.initials: D
authors.lastname: Nesic
authors.forename: C Erec
authors.initials: CE
authors.lastname: Stebbins
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry* / Q000633:toxicity*; D001427:Bacterial Toxins / Q000737:chemistry* / Q000633:toxicity; D003198:Computer Simulation; D030562:Databases, Protein; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship
chemical_list: D001426:Bacterial Proteins; D001427:Bacterial Toxins; C067044:cytolethal distending toxin