View source for 4p6f


==Crystal structure of the peptolide 12C bound to bacterial ribosome==
<StructureSection load='4p6f' size='340' side='right'caption='[[4p6f]], [[Resolution|resolution]] 3.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4p6f]] is a 20 chain structure with sequence from [https://en.wikipedia.org/wiki/Thermus_thermophilus_HB8 Thermus thermophilus HB8]. This structure supersedes the now removed PDB entries [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=4w2a 4w2a], [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=4w2b 4w2b], [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=4w2c 4w2c] and [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=4w2d 4w2d]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4P6F OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4P6F 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]] 3.6&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PAR:PAROMOMYCIN'>PAR</scene>, <scene name='pdbligand=T17:{[4-(1-{3-[(3AS,4R,7R,9R,10R,11R,13R,15R,15AR)-10-{[(2S,3R,4S,6R)-4-(DIMETHYLAMINO)-3-HYDROXY-6-METHYLTETRAHYDRO-2H-PYRAN-2-YL]OXY}-4-ETHYL-11-METHOXY-3A,7,9,11,13,15-HEXAMETHYL-2,6,8,14-TETRAOXODODECAHYDRO-2H-OXACYCLOTETRADECINO[4,3-D][1,3]OXAZOL-1(4H)-YL]PROPYL}-1H-1,2,3-TRIAZOL-4-YL)BUTANOYL]AMINO}ACETIC+ACID'>T17</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=4p6f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4p6f OCA], [https://pdbe.org/4p6f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4p6f RCSB], [https://www.ebi.ac.uk/pdbsum/4p6f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4p6f 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 ==
Despite decades of research on the bacterial ribosome, the ribosomal exit tunnel is still poorly understood. Although it has been suggested that the exit tunnel is simply a convenient route of egress for the nascent chain, specific protein sequences serve to slow the rate of translation, suggesting some degree of interaction between the nascent peptide chain and the exit tunnel. To understand how the ribosome interacts with nascent peptide sequences, we synthesized and characterized a novel class of probe molecules. These peptide-macrolide (or "peptolide") conjugates were designed to present unique peptide sequences to the exit tunnel. Biochemical and X-ray structural analyses of the interactions between these probes and the ribosome reveal interesting insights about the exit tunnel. Using translation inhibition and RNA structure probing assays, we find the exit tunnel has a relaxed preference for the directionality (N --&gt; C or C --&gt; N orientation) of the nascent peptides. Moreover, the X-ray crystal structure of one peptolide derived from a positively charged, reverse Nuclear Localization Sequence peptide, bound to the 70S bacterial ribosome, reveals that the macrolide ring of the peptolide binds in the same position as other macrolides. However, the peptide tail folds over the macrolide ring, oriented toward the peptidyl transferase center and interacting in a novel manner with 23S rRNA residue C2442 and His69 of ribosomal protein L4. These data suggest that these peptolides are viable probes for interrogating nascent peptide-exit tunnel interaction.

Macrolide-Peptide Conjugates as Probes of the Path of Travel of the Nascent Peptides through the Ribosome.,Washington AZ, Benicewicz DB, Canzoneri JC, Fagan CE, Mwakwari SC, Maehigashi T, Dunham CM, Oyelere AK ACS Chem Biol. 2014 Sep 22. PMID:25198768<ref>PMID:25198768</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4p6f" style="background-color:#fffaf0;"></div>

==See Also==
*[[Transfer RNA (tRNA)|Transfer RNA (tRNA)]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Thermus thermophilus HB8]]
[[Category: Dunham CM]]
[[Category: Fagan CE]]