6exv | pdb_00006exv

Structure of mammalian RNA polymerase II elongation complex inhibited by Alpha-amanitin

Loading... Status: waiting for Mol* initialization Structural highlights 6exv is a 10 chain structure with sequence from Sus scrofa. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.6Å Ligands: CSX, HYP, ILX, MG, TRX, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function I3LJR4_PIG DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates.[RuleBase:RU004279] Publication Abstract from PubMed RNA polymerase II (Pol II) is the central enzyme that transcribes eukaryotic protein-coding genes to produce mRNA. The mushroom toxin alpha-amanitin binds Pol II and inhibits transcription at the step of RNA chain elongation. Pol II from yeast binds alpha-amanitin with micromolar affinity, whereas metazoan Pol II enzymes exhibit nanomolar affinities. Here, we present the high-resolution cryo-EM structure of alpha-amanitin bound to and inhibited by its natural target, the mammalian Pol II elongation complex. The structure revealed that the toxin is located in a pocket previously identified in yeast Pol II, but forms additional contacts with metazoan-specific residues, which explain why its affinity to mammalian Pol II is ~3000 times higher than for yeast Pol II. Our work provides the structural basis for the inhibition of mammalian Pol II by the natural toxin alpha-amanitin and highlights that cryo-EM is well suited to studying interactions of a small molecule with its macromolecular target. Cryo-EM structure of a mammalian RNA polymerase II elongation complex inhibited by alpha-amanitin.,Liu X, Farnung L, Wigge C, Cramer P J Biol Chem. 2018 Mar 17. pii: RA118.002545. doi: 10.1074/jbc.RA118.002545. PMID:29550768 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also RNA polymerase 3D structures

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