4mex

Crystal structure of Escherichia coli RNA polymerase in complex with salinamide A

spinqualitylabelsall models 4mex, resolution 3.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4mex is a 14 chain structure with sequence from Escherichia coli K-12 and Streptomyces sp.. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.902Å Ligands: 28H, 28J, 28K, 2TL, D4P, MEA, MG, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function RPOB_ECOLI DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates.[HAMAP-Rule:MF_01321] Publication Abstract from PubMed 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 the bridge-helix N-terminal hinge necessary for nucleotide addition. The results provide a target for antibacterial drug discovery and a reagent to probe conformation and function of the bridge-helix N-terminal hinge.DOI: https://dx.doi.org/10.7554/eLife.02451.001. Transcription inhibition by the depsipeptide antibiotic salinamide A.,Degen D, Feng Y, Zhang Y, Ebright KY, Ebright YW, Gigliotti M, Vahedian-Movahed H, Mandal S, Talaue M, Connell N, Arnold E, Fenical W, Ebright RH Elife. 2014 Apr 30;3:e02451. doi: 10.7554/eLife.02451. PMID:24843001 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also RNA polymerase 3D structures Sigma factor 3D structures

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