6olf
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Human ribosome nascent chain complex (CDH1-RNC) stalled by a drug-like molecule with AA and PE tRNAs== | |
| + | <SX load='6olf' size='340' side='right' viewer='molstar' caption='[[6olf]], [[Resolution|resolution]] 3.90Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6olf]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6OLF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6OLF FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.9Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4AC:N(4)-ACETYLCYTIDINE-5-MONOPHOSPHATE'>4AC</scene>, <scene name='pdbligand=5MC:5-METHYLCYTIDINE-5-MONOPHOSPHATE'>5MC</scene>, <scene name='pdbligand=5MU:5-METHYLURIDINE+5-MONOPHOSPHATE'>5MU</scene>, <scene name='pdbligand=6MZ:N6-METHYLADENOSINE-5-MONOPHOSPHATE'>6MZ</scene>, <scene name='pdbligand=A2M:2-O-METHYLADENOSINE+5-(DIHYDROGEN+PHOSPHATE)'>A2M</scene>, <scene name='pdbligand=B8N:(2~{R})-2-azanyl-4-[5-[(2~{S},3~{R},4~{S},5~{R})-3,4-bis(oxidanyl)-5-(phosphonooxymethyl)oxolan-2-yl]-3-methyl-2,6-bis(oxidanylidene)pyrimidin-1-yl]butanoic+acid'>B8N</scene>, <scene name='pdbligand=B8Q:[(2~{R},3~{S},4~{R},5~{R})-5-(4-azanyl-3-methyl-2-oxidanylidene-4~{H}-pyrimidin-1-yl)-3,4-bis(oxidanyl)oxolan-2-yl]methyl+dihydrogen+phosphate'>B8Q</scene>, <scene name='pdbligand=E3C:[(2~{R},3~{S},4~{R},5~{R})-5-(4-azanyl-3-ethyl-2-oxidanylidene-4~{H}-pyrimidin-1-yl)-3,4-bis(oxidanyl)oxolan-2-yl]methyl+dihydrogen+phosphate'>E3C</scene>, <scene name='pdbligand=M7A:[(2~{R},3~{S},4~{R},5~{R})-5-(6-azanyl-7-methyl-8~{H}-purin-9-yl)-3,4-bis(oxidanyl)oxolan-2-yl]methyl+dihydrogen+phosphate'>M7A</scene>, <scene name='pdbligand=MA6:6N-DIMETHYLADENOSINE-5-MONOPHOSHATE'>MA6</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MVM:~{N}-(3-chloranylpyridin-2-yl)-~{N}-[(3~{R})-piperidin-3-yl]-4-([1,2,3]triazolo[4,5-b]pyridin-3-yl)benzamide'>MVM</scene>, <scene name='pdbligand=OMC:O2-METHYLYCYTIDINE-5-MONOPHOSPHATE'>OMC</scene>, <scene name='pdbligand=OMG:O2-METHYLGUANOSINE-5-MONOPHOSPHATE'>OMG</scene>, <scene name='pdbligand=OMU:O2-METHYLURIDINE+5-MONOPHOSPHATE'>OMU</scene>, <scene name='pdbligand=PSU:PSEUDOURIDINE-5-MONOPHOSPHATE'>PSU</scene>, <scene name='pdbligand=UR3:3-METHYLURIDINE-5-MONOPHOSHATE'>UR3</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6olf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6olf OCA], [https://pdbe.org/6olf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6olf RCSB], [https://www.ebi.ac.uk/pdbsum/6olf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6olf ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/RS5_HUMAN RS5_HUMAN] | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The drug-like molecule PF-06446846 (PF846) binds the human ribosome and selectively blocks the translation of a small number of proteins by an unknown mechanism. In structures of PF846-stalled human ribosome nascent chain complexes, PF846 binds in the ribosome exit tunnel in a eukaryotic-specific pocket formed by 28S ribosomal RNA, and alters the path of the nascent polypeptide chain. PF846 arrests the translating ribosome in the rotated state of translocation, in which the peptidyl-transfer RNA 3'-CCA end is improperly docked in the peptidyl transferase center. Selections of messenger RNAs from mRNA libraries using translation extracts reveal that PF846 can stall translation elongation, arrest termination or even enhance translation, depending on nascent chain sequence context. These results illuminate how a small molecule selectively targets translation by the human ribosome, and provides a foundation for developing small molecules that modulate the production of proteins of therapeutic interest. | ||
| - | + | Structural basis for selective stalling of human ribosome nascent chain complexes by a drug-like molecule.,Li W, Ward FR, McClure KF, Chang ST, Montabana E, Liras S, Dullea RG, Cate JHD Nat Struct Mol Biol. 2019 Jun;26(6):501-509. doi: 10.1038/s41594-019-0236-8. Epub, 2019 Jun 3. PMID:31160784<ref>PMID:31160784</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: Cate | + | <div class="pdbe-citations 6olf" style="background-color:#fffaf0;"></div> |
| - | [[Category: Li | + | |
| + | ==See Also== | ||
| + | *[[Ribosome 3D structures|Ribosome 3D structures]] | ||
| + | *[[3D sructureseceptor for activated protein kinase C 1|3D sructureseceptor for activated protein kinase C 1]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </SX> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Cate JHD]] | ||
| + | [[Category: Li W]] | ||
Current revision
Human ribosome nascent chain complex (CDH1-RNC) stalled by a drug-like molecule with AA and PE tRNAs
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