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==Crystal structure of the 30S ribosome in complex with compound 39== | |||
<StructureSection load='4b3t' size='340' side='right'caption='[[4b3t]], [[Resolution|resolution]] 3.00Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4b3t]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Thermus_thermophilus_HB8 Thermus thermophilus HB8]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4B3T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4B3T 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]] 3Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3TS:(2S,3S,4R,5R,6R)-2-(AMINOMETHYL)-5-AZANYL-6-[(2R,3S,4R,5S)-5-[(1R,2R,3S,5R,6S)-3,5-BIS(AZANYL)-2-[(2S,3R,4R,5S,6R)-3-AZANYL-5-[(4-CHLOROPHENYL)METHOXY]-6-(HYDROXYMETHYL)-4-OXIDANYL-OXAN-2-YL]OXY-6-OXIDANYL-CYCLOHEXYL]OXY-2-(HYDROXYMETHYL)-4-OXIDANYL-OXOLAN-3-YL]OXY-OXANE-3,4-DIOL'>3TS</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=4b3t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4b3t OCA], [https://pdbe.org/4b3t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4b3t RCSB], [https://www.ebi.ac.uk/pdbsum/4b3t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4b3t ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/RS2_THET8 RS2_THET8] Spans the head-body hinge region of the 30S subunit. Is loosely associated with the 30S subunit.[HAMAP-Rule:MF_00291_B] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Clinical use of 2-deoxystreptamine aminoglycoside antibiotics, which target the bacterial ribosome, is compromised by adverse effects related to limited drug selectivity. Here we present a series of 4',6'-O-acetal and 4'-O-ether modifications on glucopyranosyl ring I of aminoglycosides. Chemical modifications were guided by measuring interactions between the compounds synthesized and ribosomes harbouring single point mutations in the drug-binding site, resulting in aminoglycosides that interact poorly with the drug-binding pocket of eukaryotic mitochondrial or cytosolic ribosomes. Yet, these compounds largely retain their inhibitory activity for bacterial ribosomes and show antibacterial activity. Our data indicate that 4'-O-substituted aminoglycosides possess increased selectivity towards bacterial ribosomes and little activity for any of the human drug-binding pockets. | |||
4'-O-substitutions determine selectivity of aminoglycoside antibiotics.,Perez-Fernandez D, Shcherbakov D, Matt T, Leong NC, Kudyba I, Duscha S, Boukari H, Patak R, Dubbaka SR, Lang K, Meyer M, Akbergenov R, Freihofer P, Vaddi S, Thommes P, Ramakrishnan V, Vasella A, Bottger EC Nat Commun. 2014 Jan 28;5:3112. doi: 10.1038/ncomms4112. PMID:24473108<ref>PMID:24473108</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4b3t" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Ribosomal protein THX 3D structures|Ribosomal protein THX 3D structures]] | |||
*[[Ribosome 3D structures|Ribosome 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Thermus thermophilus HB8]] | |||
[[Category: Akbergenov R]] | |||
[[Category: Bottger EC]] | |||
[[Category: Boukari H]] | |||
[[Category: Duscha S]] | |||
[[Category: Freihofer P]] | |||
[[Category: Kudyba I]] | |||
[[Category: Lang K]] | |||
[[Category: Matt T]] | |||
[[Category: Meyer M]] | |||
[[Category: Nandurikar RS]] | |||
[[Category: Ng CL]] | |||
[[Category: Patak R]] | |||
[[Category: Perez-Fernandez D]] | |||
[[Category: Ramakrishnan V]] | |||
[[Category: Reddy MSK]] | |||
[[Category: Shcherbakov D]] | |||
[[Category: Vasella A]] | |||
Latest revision as of 14:42, 20 December 2023
Crystal structure of the 30S ribosome in complex with compound 39Crystal structure of the 30S ribosome in complex with compound 39
Structural highlights
FunctionRS2_THET8 Spans the head-body hinge region of the 30S subunit. Is loosely associated with the 30S subunit.[HAMAP-Rule:MF_00291_B] Publication Abstract from PubMedClinical use of 2-deoxystreptamine aminoglycoside antibiotics, which target the bacterial ribosome, is compromised by adverse effects related to limited drug selectivity. Here we present a series of 4',6'-O-acetal and 4'-O-ether modifications on glucopyranosyl ring I of aminoglycosides. Chemical modifications were guided by measuring interactions between the compounds synthesized and ribosomes harbouring single point mutations in the drug-binding site, resulting in aminoglycosides that interact poorly with the drug-binding pocket of eukaryotic mitochondrial or cytosolic ribosomes. Yet, these compounds largely retain their inhibitory activity for bacterial ribosomes and show antibacterial activity. Our data indicate that 4'-O-substituted aminoglycosides possess increased selectivity towards bacterial ribosomes and little activity for any of the human drug-binding pockets. 4'-O-substitutions determine selectivity of aminoglycoside antibiotics.,Perez-Fernandez D, Shcherbakov D, Matt T, Leong NC, Kudyba I, Duscha S, Boukari H, Patak R, Dubbaka SR, Lang K, Meyer M, Akbergenov R, Freihofer P, Vaddi S, Thommes P, Ramakrishnan V, Vasella A, Bottger EC Nat Commun. 2014 Jan 28;5:3112. doi: 10.1038/ncomms4112. PMID:24473108[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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