2ogn
From Proteopedia
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| - | [[Image:2ogn.gif|left|200px]]<br /><applet load="2ogn" size="350" color="white" frame="true" align="right" spinBox="true" | ||
| - | caption="2ogn, resolution 3.56Å" /> | ||
| - | '''The crystal structure of the large ribosomal subunit from Deinococcus radiodurans complexed with the pleuromutilin derivative SB-280080'''<br /> | ||
| - | == | + | ==The crystal structure of the large ribosomal subunit from Deinococcus radiodurans complexed with the pleuromutilin derivative SB-280080== |
| + | <StructureSection load='2ogn' size='340' side='right'caption='[[2ogn]], [[Resolution|resolution]] 3.56Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[2ogn]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Deinococcus_radiodurans Deinococcus radiodurans]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2OGN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2OGN 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]] 3.56Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=G80:(3AS,4R,5S,6S,8R,9R,9AR,10R)-5-HYDROXY-4,6,9,10-TETRAMETHYL-1-OXO-6-VINYLDECAHYDRO-3A,9-PROPANOCYCLOPENTA[8]ANNULEN-8-YL+(PIPERIDIN-4-YLTHIO)ACETATE'>G80</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=2ogn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ogn OCA], [https://pdbe.org/2ogn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ogn RCSB], [https://www.ebi.ac.uk/pdbsum/2ogn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ogn ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/RL3_DEIRA RL3_DEIRA] One of the primary rRNA binding proteins, it binds directly near the 3'-end of the 23S rRNA, where it nucleates assembly of the 50S subunit (By similarity).[HAMAP-Rule:MF_01325_B] | ||
| + | == 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/og/2ogn_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/main_output.php?pdb_ID=2ogn ConSurf]. | ||
| + | <div style="clear:both"></div> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
New insights into functional flexibility at the peptidyl transferase center (PTC) and its vicinity were obtained by analysis of pleuromutilins binding modes to the ribosome. The crystal structures of Deinococcus radiodurans large ribosomal subunit complexed with each of three pleuromutilin derivatives: retapamulin (SB-275833), SB-280080, and SB-571519, show that all bind to the PTC with their core oriented similarly at the A-site and their C14 extensions pointing toward the P-site. Except for an H-bond network with a single nucleotide, G2061, which involves the essential keto group of all three compounds, only minor hydrophobic contacts are formed between the pleuromutilin C14 extensions and any ribosomal component, consistent with the PTC tolerance to amino acid diversity. Efficient drug binding mode is attained by a mechanism based on induced-fit motions exploiting the ribosomal intrinsic functional flexibility and resulting in conformational rearrangements that seal the pleuromutilin-binding pocket and tightens it up. Comparative studies identified a network of remote interactions around the PTC, indicating that pleuromutilins selectivity is acquired by nonconserved nucleotides residing in the PTC vicinity, in a fashion resembling allosterism. Likewise, pleuromutilin resistant mechanisms involve nucleotides residing in the environs of the binding pocket, consistent with their slow resistance-development rates. | New insights into functional flexibility at the peptidyl transferase center (PTC) and its vicinity were obtained by analysis of pleuromutilins binding modes to the ribosome. The crystal structures of Deinococcus radiodurans large ribosomal subunit complexed with each of three pleuromutilin derivatives: retapamulin (SB-275833), SB-280080, and SB-571519, show that all bind to the PTC with their core oriented similarly at the A-site and their C14 extensions pointing toward the P-site. Except for an H-bond network with a single nucleotide, G2061, which involves the essential keto group of all three compounds, only minor hydrophobic contacts are formed between the pleuromutilin C14 extensions and any ribosomal component, consistent with the PTC tolerance to amino acid diversity. Efficient drug binding mode is attained by a mechanism based on induced-fit motions exploiting the ribosomal intrinsic functional flexibility and resulting in conformational rearrangements that seal the pleuromutilin-binding pocket and tightens it up. Comparative studies identified a network of remote interactions around the PTC, indicating that pleuromutilins selectivity is acquired by nonconserved nucleotides residing in the PTC vicinity, in a fashion resembling allosterism. Likewise, pleuromutilin resistant mechanisms involve nucleotides residing in the environs of the binding pocket, consistent with their slow resistance-development rates. | ||
| - | + | Induced-fit tightens pleuromutilins binding to ribosomes and remote interactions enable their selectivity.,Davidovich C, Bashan A, Auerbach-Nevo T, Yaggie RD, Gontarek RR, Yonath A Proc Natl Acad Sci U S A. 2007 Mar 13;104(11):4291-6. Epub 2007 Mar 8. PMID:17360517<ref>PMID:17360517</ref> | |
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| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | <div class="pdbe-citations 2ogn" style="background-color:#fffaf0;"></div> | |
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| - | + | ==See Also== | |
| + | *[[Ribosomal protein L3|Ribosomal protein L3]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Deinococcus radiodurans]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Auerbach-Nevo T]] | ||
| + | [[Category: Bashan A]] | ||
| + | [[Category: Davidovich C]] | ||
| + | [[Category: Yonath A]] | ||
Current revision
The crystal structure of the large ribosomal subunit from Deinococcus radiodurans complexed with the pleuromutilin derivative SB-280080
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