{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Degen D"],"funding":["Howard Hughes Medical Institute","NIAID NIH HHS","National Institutes of Health","NIGMS NIH HHS"],"pagination":["e02451"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC4029172"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["3"],"pubmed_abstract":["We report that bacterial RNA polymerase (RNAP) is the functional cellular target of the depsipeptide antibiotic salinamide A (Sal), and we report that Sal inhibits RNAP through a novel binding site and mechanism. We show that Sal inhibits RNA synthesis in cells and that mutations that confer Sal-resistance map to RNAP genes. We show that Sal interacts with the RNAP active-center 'bridge-helix cap' comprising the 'bridge-helix N-terminal hinge', 'F-loop', and 'link region'. We show that Sal inhibits nucleotide addition in transcription initiation and elongation. We present a crystal structure that defines interactions between Sal and RNAP and effects of Sal on RNAP conformation. We propose that Sal functions by binding to the RNAP bridge-helix cap and preventing conformational changes of th"],"journal":["eLife"],"pubmed_title":["Transcription inhibition by the depsipeptide antibiotic salinamide A."],"pmcid":["PMC4029172"],"funding_grant_id":["GM084350","R01 AI104660","P41 GM111244","GM041376","P41 GM103485","R01 GM084350","R01 GM041376","R01 AI072766","AI072766","R37 GM041376","AI104660"],"pubmed_authors":["Fenical W","Feng Y","Talaue M","Ebright KY","Gigliotti M","Degen D","Mandal S","Ebright RH","Zhang Y","Connell N","Vahedian-Movahed H","Arnold E","Ebright YW"],"additional_accession":[]},"is_claimable":false,"name":"Transcription inhibition by the depsipeptide antibiotic salinamide A.","description":"We report that bacterial RNA polymerase (RNAP) is the functional cellular target of the depsipeptide antibiotic salinamide A (Sal), and we report that Sal inhibits RNAP through a novel binding site and mechanism. We show that Sal inhibits RNA synthesis in cells and that mutations that confer Sal-resistance map to RNAP genes. We show that Sal interacts with the RNAP active-center 'bridge-helix cap' comprising the 'bridge-helix N-terminal hinge', 'F-loop', and 'link region'. We show that Sal inhibits nucleotide addition in transcription initiation and elongation. We present a crystal structure that defines interactions between Sal and RNAP and effects of Sal on RNAP conformation. We propose that Sal functions by binding to the RNAP bridge-helix cap and preventing conformational changes of th","dates":{"release":"2014-01-01T00:00:00Z","publication":"2014 Apr","modification":"2026-05-01T23:14:22.947Z","creation":"2019-03-27T00:14:29Z"},"accession":"S-EPMC4029172","cross_references":{"pubmed":["24843001"],"doi":["10.7554/eLife.02451"]}}