4u27
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of the E. coli ribosome bound to flopristin and linopristin.== | |
| + | <StructureSection load='4u27' size='340' side='right'caption='[[4u27]], [[Resolution|resolution]] 2.80Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[4u27]] is a 20 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_K-12 Escherichia coli K-12] and [https://en.wikipedia.org/wiki/Escherichia_coli_str._K-12_substr._MDS42 Escherichia coli str. K-12 substr. MDS42]. This structure supersedes the now removed PDB entries [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=4tpc 4tpc], [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=4tpd 4tpd], [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=4tpe 4tpe] and [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=4tpf 4tpf]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4U27 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4U27 FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.8Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=004:(2S)-AMINO(PHENYL)ETHANOIC+ACID'>004</scene>, <scene name='pdbligand=04X:(2S)-5-(MORPHOLIN-4-YLMETHYL)-1,2,3,6-TETRAHYDROPYRIDINE-2-CARBOXYLIC+ACID'>04X</scene>, <scene name='pdbligand=DBB:D-ALPHA-AMINOBUTYRIC+ACID'>DBB</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MHU:4-N,N-(DIMETHYLAMINO)-L-PHENYLALANINE'>MHU</scene>, <scene name='pdbligand=MHW:3-HYDROXYPICOLINIC+ACID'>MHW</scene>, <scene name='pdbligand=VIF:FLOPRISTIN'>VIF</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=4u27 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4u27 OCA], [https://pdbe.org/4u27 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4u27 RCSB], [https://www.ebi.ac.uk/pdbsum/4u27 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4u27 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/RS19_ECOLI RS19_ECOLI] In the E.coli 70S ribosome in the initiation state (PubMed:12809609) it has been modeled to contact the 23S rRNA of the 50S subunit forming part of bridge B1a; this bridge is broken in the model with bound EF-G. The 23S rRNA contact site in bridge B1a is modeled to differ in different ribosomal states (PubMed:12859903), contacting alternately S13 or S19. In the 3.5 angstroms resolved ribosome structures (PubMed:16272117) the contacts between L5, S13 and S19 bridge B1b are different, confirming the dynamic nature of this interaction. Bridge B1a is not visible in the crystallized ribosomes due to 23S rRNA disorder.[HAMAP-Rule:MF_00531] Protein S19 forms a complex with S13 that binds strongly to the 16S ribosomal RNA. Contacts the A site tRNA.[HAMAP-Rule:MF_00531] | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Streptogramin antibiotics are divided into type A and B streptogramins, which in combination can act synergistically. We compared the molecular interactions of the streptogramin combinations Synercid (type A: dalfopristin, type B: quinupristin) and NXL 103 (type A: flopristin, type B: linopristin) with the Escherichia coli 70S ribosome by x-ray crystallography. We further analyzed the activity of the streptogramin components individually and in combination. Streptogramin A and B components in Synercid and NXL 103 exhibit synergistic antimicrobial activity against certain pathogenic bacteria. However, in transcription-coupled translation assays, only combinations that include dalfopristin, the streptogramin A component of Synercid, show synergy. Notably, the diethylaminoethylsulfonyl group in dalfopristin reduces its activity, but is the basis for synergy in transcription-coupled translation assays before its rapid hydrolysis from the depsipeptide core. Replacement of the diethylaminoethylsulfonyl group in dalfopristin by a non-hydrolyzable group may therefore be beneficial for synergy. The absence of general streptogramin synergy in transcription-coupled translation assays suggests that synergistic antimicrobial activity of streptogramins can occur independently of streptogramin effects on translation. | ||
| - | + | Synergy of streptogramin antibiotics occurs independently of their effects on translation.,Noeske J, Huang J, Olivier NB, Giacobbe RA, Zambrowski M, Cate JH Antimicrob Agents Chemother. 2014 Jun 23. pii: AAC.03389-14. PMID:24957822<ref>PMID:24957822</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| + | </div> | ||
| + | <div class="pdbe-citations 4u27" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Ribosome 3D structures|Ribosome 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Escherichia coli K-12]] | ||
| + | [[Category: Escherichia coli str. K-12 substr. MDS42]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Cate JHD]] | ||
| + | [[Category: Giacobbe RA]] | ||
| + | [[Category: Huang J]] | ||
| + | [[Category: Noeske J]] | ||
| + | [[Category: Olivier NB]] | ||
| + | [[Category: Zambrowski M]] | ||
Current revision
Crystal structure of the E. coli ribosome bound to flopristin and linopristin.
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