title: The binding site and mechanism of the RNA polymerase inhibitor tagetitoxin: an issue open to debate.
abstract: In a recent paper in the Journal of Biological Chemistry, Artsimovitch et al. report a major revision of a crystallographic model and proposed mechanism of the RNA polymerase inhibitor, tagetitoxin. This reassessment is based on theoretical modeling using molecular dynamics simulations. Here, we argue that this theoretical model contradicts experimental results and a published crystal structure cannot exclude several mechanistically distinct alternative models and does not support some major conclusions. We conclude that understanding the tagetitoxin mechanism is beyond the reach of currently available computational simulations and must await input from high-resolution crystal structures of tagetitoxin bound to elongation complex, extensive biochemical studies, or both.
authors.affiliation: Department of Biochemistry and Molecular Genetics, Schools of Medicine and Dentistry, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Sergiy
authors.initials: S
authors.lastname: Klyuyev
authors.forename: Dmitry G
authors.initials: DG
authors.lastname: Vassylyev
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D012321:DNA-Directed RNA Polymerases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D003998:Dicarboxylic Acids / Q000737:chemistry / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism*; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D009943:Organophosphorus Compounds / Q000737:chemistry / Q000378:metabolism*; D017434:Protein Structure, Tertiary
chemical_list: D003998:Dicarboxylic Acids; D004791:Enzyme Inhibitors; D009943:Organophosphorus Compounds; C062221:tagetitoxin; D012321:DNA-Directed RNA Polymerases