View source for 5jvh


==The crystal structure large ribosomal subunit (50S) of Deinococcus radiodurans in complex with evernimicin==
<StructureSection load='5jvh' size='340' side='right'caption='[[5jvh]], [[Resolution|resolution]] 3.58&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5jvh]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Deinococcus_radiodurans_R1 Deinococcus radiodurans R1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5JVH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5JVH 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]] 3.58&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6O1:EVERNIMICIN'>6O1</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=5jvh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5jvh OCA], [https://pdbe.org/5jvh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5jvh RCSB], [https://www.ebi.ac.uk/pdbsum/5jvh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5jvh ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/RL13_DEIRA RL13_DEIRA] This protein is one of the early assembly proteins of the 50S ribosomal subunit (By similarity). Binds to the 23S rRNA.[HAMAP-Rule:MF_01366_B]
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== Publication Abstract from PubMed ==
Two structurally unique ribosomal antibiotics belonging to the orthosomycin family, avilamycin and evernimicin, possess activity against Enterococci, Staphylococci, and Streptococci, and other Gram-positive bacteria. Here, we describe the high-resolution crystal structures of the eubacterial large ribosomal subunit in complex with them. Their extended binding sites span the A-tRNA entrance corridor, thus inhibiting protein biosynthesis by blocking the binding site of the A-tRNA elbow, a mechanism not shared with other known antibiotics. Along with using the ribosomal components that bind and discriminate the A-tRNA-namely, ribosomal RNA (rRNA) helices H89, H91, and ribosomal proteins (rProtein) uL16-these structures revealed novel interactions with domain 2 of the CTC protein, a feature typical to various Gram-positive bacteria. Furthermore, analysis of these structures explained how single nucleotide mutations and methylations in helices H89 and H91 confer resistance to orthosomycins and revealed the sequence variations in 23S rRNA nucleotides alongside the difference in the lengths of the eukaryotic and prokaryotic alpha1 helix of protein uL16 that play a key role in the selectivity of those drugs. The accurate interpretation of the crystal structures that could be performed beyond that recently reported in cryo-EM models provide structural insights that may be useful for the design of novel pathogen-specific antibiotics, and for improving the potency of orthosomycins. Because both drugs are extensively metabolized in vivo, their environmental toxicity is very low, thus placing them at the frontline of drugs with reduced ecological hazards.

Avilamycin and evernimicin induce structural changes in rProteins uL16 and CTC that enhance the inhibition of A-site tRNA binding.,Krupkin M, Wekselman I, Matzov D, Eyal Z, Diskin Posner Y, Rozenberg H, Zimmerman E, Bashan A, Yonath A Proc Natl Acad Sci U S A. 2016 Nov 1;113(44):E6796-E6805. Epub 2016 Oct 19. PMID:27791159<ref>PMID:27791159</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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== References ==
<references/>
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</StructureSection>
[[Category: Deinococcus radiodurans R1]]
[[Category: Large Structures]]
[[Category: Yonath A]]