View source for 1k83

==Crystal Structure of Yeast RNA Polymerase II Complexed with the Inhibitor Alpha Amanitin==
<StructureSection load='1k83' size='340' side='right' caption='[[1k83]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1k83]] is a 11 chain structure with sequence from [http://en.wikipedia.org/wiki/Amanita_phalloides Amanita phalloides] and [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. The April 2003 RCSB PDB [http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''RNA Polymerase''  by David S. Goodsell is [http://dx.doi.org/10.2210/rcsb_pdb/mom_2003_4 10.2210/rcsb_pdb/mom_2003_4]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1K83 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1K83 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CSX:S-OXY+CYSTEINE'>CSX</scene>, <scene name='pdbligand=HYP:4-HYDROXYPROLINE'>HYP</scene>, <scene name='pdbligand=ILX:4,5-DIHYDROXYISOLEUCINE'>ILX</scene>, <scene name='pdbligand=TRX:6-HYDROXYTRYPTOPHAN'>TRX</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1i50|1i50]], [[2vum|2vum]], [[3cqz|3cqz]]</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/DNA-directed_RNA_polymerase DNA-directed RNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.6 2.7.7.6] </span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1k83 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1k83 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1k83 RCSB], [http://www.ebi.ac.uk/pdbsum/1k83 PDBsum]</span></td></tr>
</table>
== Function ==
[[http://www.uniprot.org/uniprot/AMATX_AMAPH AMATX_AMAPH]] Major toxin from Amanita phalloideae. Acts by binding non-competitively to RNA polymerase II and greatly slowing the elongation of transcripts from target promoters.<ref>PMID:4865716</ref> <ref>PMID:363352</ref> <ref>PMID:7642577</ref> <ref>PMID:8702941</ref>  [[http://www.uniprot.org/uniprot/RPB3_YEAST RPB3_YEAST]] DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Component of RNA polymerase II which synthesizes mRNA precursors and many functional non-coding RNAs. Pol II is the central component of the basal RNA polymerase II transcription machinery. It is composed of mobile elements that move relative to each other. RPB3 is part of the core element with the central large cleft and the clamp element that moves to open and close the cleft. Seems to be involved in transcription termination. [[http://www.uniprot.org/uniprot/RPB9_YEAST RPB9_YEAST]] DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Component of RNA polymerase II which synthesizes mRNA precursors and many functional non-coding RNAs. Pol II is the central component of the basal RNA polymerase II transcription machinery. It is composed of mobile elements that move relative to each other. RPB9 is part of the upper jaw surrounding the central large cleft and thought to grab the incoming DNA template. Involved in the regulation of transcription elongation. Involved in DNA repair of damage in the transcribed strand. Mediates a transcription-coupled repair (TCR) subpathway of nucleotide excision repair (NER).<ref>PMID:12411509</ref>  [[http://www.uniprot.org/uniprot/RPB2_YEAST RPB2_YEAST]] DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Second largest component of RNA polymerases II which synthesizes mRNA precursors and many functional non-coding RNAs. Proposed to contribute to the polymerase catalytic activity and forms the polymerase active center together with the largest subunit. Pol II is the central component of the basal RNA polymerase II transcription machinery. During a transcription cycle, Pol II, general transcription factors and the Mediator complex assemble as the preinitiation complex (PIC) at the promoter. 11-15 base pairs of DNA surrounding the transcription start site are melted and the single stranded DNA template strand of the promoter is positioned deeply within the central active site cleft of Pol II to form the open complex. After synthesis of about 30 bases of RNA, Pol II releases its contacts with the core promoter and the rest of the transcription machinery (promoter clearance) and enters the stage of transcription elongation in which it moves on the template as the transcript elongates. Pol II appears to oscillate between inactive and active conformations at each step of nucleotide addition. Pol II is composed of mobile elements that move relative to each other. The core element with the central large cleft comprises RPB3, RBP10, RPB11, RPB12 and regions of RPB1 and RPB2 forming the active center. The clamp element (portions of RPB1, RPB2 and RPB3) is connected to the core through a set of flexible switches and moves to open and close the cleft. The cleft is surrounded by jaws: an upper jaw formed by portions of RBP1, RPB2 and RPB9, and a lower jaw. The jaws are thought to grab the incoming DNA template. The fork loop 1 (RPB2) interacts with the RNA-DNA hybrid, possibly stabilizing it. [[http://www.uniprot.org/uniprot/RPB1_YEAST RPB1_YEAST]] DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Largest and catalytic component of RNA polymerase II which synthesizes mRNA precursors and many functional non-coding RNAs. Forms the polymerase active center together with the second largest subunit. Pol II is the central component of the basal RNA polymerase II transcription machinery. During a transcription cycle, Pol II, general transcription factors and the Mediator complex assemble as the preinitiation complex (PIC) at the promoter. 11-15 base pairs of DNA surrounding the transcription start site are melted and the single stranded DNA template strand of the promoter is positioned deeply within the central active site cleft of Pol II to form the open complex. After synthesis of about 30 bases of RNA, Pol II releases its contacts with the core promoter and the rest of the transcription machinery (promoter clearance) and enters the stage of transcription elongation in which it moves on the template as the transcript elongates. Pol II appears to oscillate between inactive and active conformations at each step of nucleotide addition. Elongation is influenced by the phosphorylation status of the C-terminal domain (CTD) of Pol II largest subunit (RPB1), which serves as a platform for assembly of factors that regulate transcription initiation, elongation, termination and mRNA processing. Pol II is composed of mobile elements that move relative to each other. The core element with the central large cleft comprises RPB3, RBP10, RPB11, RPB12 and regions of RPB1 and RPB2 forming the active center. The clamp element (portions of RPB1, RPB2 and RPB3) is connected to the core through a set of flexible switches and moves to open and close the cleft. A bridging helix emanates from RPB1 and crosses the cleft near the catalytic site and is thought to promote translocation of Pol II by acting as a ratchet that moves the RNA-DNA hybrid through the active site by switching from straight to bent conformations at each step of nucleotide addition. In elongating Pol II, the lid loop (RPB1) appears to act as a wedge to drive apart the DNA and RNA strands at the upstream end of the transcription bubble and guide the RNA strand toward the RNA exit groove located near the base of the largely unstructured CTD domain of RPB1. The rudder loop (RPB1) interacts with single stranded DNA after separation from the RNA strand, likely preventing reassociation with the exiting RNA. The cleft is surrounded by jaws: an upper jaw formed by portions of RBP1, RPB2 and RPB9, and a lower jaw, formed by RPB5 and portions of RBP1. The jaws are thought to grab the incoming DNA template, mainly by RPB5 direct contacts to DNA. 
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/k8/1k83_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
<div style="clear:both"></div>
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== Publication Abstract from PubMed ==
The structure of RNA polymerase II in a complex with the inhibitor alpha-amanitin has been determined by x-ray crystallography. The structure of the complex indicates the likely basis of inhibition and gives unexpected insight into the transcription mechanism.

Structural basis of transcription: alpha-amanitin-RNA polymerase II cocrystal at 2.8 A resolution.,Bushnell DA, Cramer P, Kornberg RD Proc Natl Acad Sci U S A. 2002 Feb 5;99(3):1218-22. Epub 2002 Jan 22. PMID:11805306<ref>PMID:11805306</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Amanita phalloides]]
[[Category: DNA-directed RNA polymerase]]
[[Category: RCSB PDB Molecule of the Month]]
[[Category: RNA Polymerase]]
[[Category: Saccharomyces cerevisiae]]
[[Category: Bushnell, D A]]
[[Category: Cramer, P]]
[[Category: Kornberg, R D]]
[[Category: Alpha amanitin]]
[[Category: Dna binding]]
[[Category: Inhibitor]]
[[Category: Phosphoprotein]]
[[Category: Polymerase]]
[[Category: Toxin]]
[[Category: Transcription]]
[[Category: Transcription-toxin complex]]
[[Category: Transferase]]
[[Category: Ubl transcription-toxin complex]]
[[Category: Zinc-finger]]