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| | <StructureSection load='5jvg' size='340' side='right'caption='[[5jvg]], [[Resolution|resolution]] 3.43Å' scene=''> | | <StructureSection load='5jvg' size='340' side='right'caption='[[5jvg]], [[Resolution|resolution]] 3.43Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5jvg]] is a 29 chain structure with sequence from [http://en.wikipedia.org/wiki/Deira Deira], [http://en.wikipedia.org/wiki/Deinococcus_radiodurans Deinococcus radiodurans] and [http://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=5JVG OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5JVG FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5jvg]] 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=5JVG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5JVG FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6NO:AVILAMYCIN'>6NO</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>, <scene name='pdbligand=SPD:SPERMIDINE'>SPD</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.428Å</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5jvg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5jvg OCA], [http://pdbe.org/5jvg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5jvg RCSB], [http://www.ebi.ac.uk/pdbsum/5jvg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5jvg ProSAT]</span></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6NO:AVILAMYCIN'>6NO</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>, <scene name='pdbligand=SPD:SPERMIDINE'>SPD</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=5jvg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5jvg OCA], [https://pdbe.org/5jvg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5jvg RCSB], [https://www.ebi.ac.uk/pdbsum/5jvg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5jvg ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/RL15_DEIRA RL15_DEIRA]] Binds to the 23S rRNA.[HAMAP-Rule:MF_01341_B] [[http://www.uniprot.org/uniprot/RL25_DEIRA RL25_DEIRA]] This is one of 3 proteins that mediate the attachment of the 5S rRNA onto the large ribosomal subunit. This protein has three domains. The N-terminal one is bound on the solvent face, the middle domain fills the space between the 5S rRNA and the L11 arm contacting the 23S rRNA while the C-terminal domain is on the edge of the intersubunit interface and contacts the A site. The protein conformation changes upon binding of a tRNA mimic to the A site, although the mimic does not interact directly with CTC itself, consistent with CTCs presumed role in moderating A site binding.[HAMAP-Rule:MF_01334] [[http://www.uniprot.org/uniprot/RL6_DEIRA RL6_DEIRA]] It is located near the subunit interface in the base of the L7/L12 stalk, and near the tRNA binding site of the peptidyltransferase center (By similarity). This protein binds to the 23S rRNA, and is important in its secondary structure.[HAMAP-Rule:MF_01365] [[http://www.uniprot.org/uniprot/RL32_DEIRA RL32_DEIRA]] Forms a cluster with L17 and L22, and with L22, a pair of "tweezers" that hold together all the domains of the 23S rRNA. Interacts with the antibiotic troleandomycin which blocks the peptide exit tunnel.[HAMAP-Rule:MF_00340] [[http://www.uniprot.org/uniprot/RL21_DEIRA RL21_DEIRA]] Binds directly to 23S rRNA, probably serving to organize its structure.[HAMAP-Rule:MF_01363] [[http://www.uniprot.org/uniprot/RL27_DEIRA RL27_DEIRA]] Binds the 5S and 23S rRNAs and also the tRNA in the P site.[HAMAP-Rule:MF_00539] [[http://www.uniprot.org/uniprot/RL22_DEIRA RL22_DEIRA]] This protein binds specifically to 23S rRNA; its binding is stimulated by other ribosomal proteins, e.g. L4, L17, and L20. It is important during the early stages of 50S assembly. It makes multiple contacts with different domains of the 23S rRNA in the assembled 50S subunit and ribosome (By similarity).[HAMAP-Rule:MF_01331_B] The globular domain of the protein is located by the polypeptide exit tunnel on the outside of the subunit while an extended beta-hairpin forms part of the wall of the tunnel. Forms a pair of "tweezers" with L32 that hold together two different domains of the 23S rRNA. Interacts with the tunnel-blocking modified macrolide azithromycin. Upon binding of the macrolide troleadomycin to the ribosome, the tip of the beta-hairpin is displaced, which severely restricts the tunnel. This and experiments in E.coli have led to the suggestion that it is part of the gating mechanism involved in translation arrest in the absence of the protein export system.[HAMAP-Rule:MF_01331_B] [[http://www.uniprot.org/uniprot/RL20_DEIRA RL20_DEIRA]] Binds directly to 23S rRNA, probably serving to organize its structure.[HAMAP-Rule:MF_00382] [[http://www.uniprot.org/uniprot/RL17_DEIRA RL17_DEIRA]] Binds to the 23S rRNA.[HAMAP-Rule:MF_01368] [[http://www.uniprot.org/uniprot/RL35_DEIRA RL35_DEIRA]] Binds the 23S rRNA.[HAMAP-Rule:MF_00514] [[http://www.uniprot.org/uniprot/RL33_DEIRA RL33_DEIRA]] Binds the 23S rRNA and the E site tRNA.[HAMAP-Rule:MF_00294] [[http://www.uniprot.org/uniprot/RL30_DEIRA RL30_DEIRA]] Binds the 5S and 23S rRNAs.[HAMAP-Rule:MF_01371] [[http://www.uniprot.org/uniprot/RL5_DEIRA RL5_DEIRA]] This is 1 of the proteins that binds and probably mediates the attachment of the 5S RNA into the large ribosomal subunit, where it forms part of the central protuberance. In the 70S ribosome it contacts protein S13 of the 30S subunit (bridge B1b), connecting the 2 subunits; this bridge is implicated in subunit movement (By similarity). Contacts the P site tRNA; the 5S rRNA and some of its associated proteins might help stabilize positioning of ribosome-bound tRNAs.[HAMAP-Rule:MF_01333_B] [[http://www.uniprot.org/uniprot/RL34_DEIRA RL34_DEIRA]] Binds the 23S rRNA.[HAMAP-Rule:MF_00391] [[http://www.uniprot.org/uniprot/RL2_DEIRA RL2_DEIRA]] One of the primary rRNA binding proteins. Required for association of the 30S and 50S subunits to form the 70S ribosome, for tRNA binding and peptide bond formation. It has been suggested to have peptidyltransferase activity; this is somewhat controversial. Makes several contacts with the 16S rRNA in the 70S ribosome (By similarity).[HAMAP-Rule:MF_01320_B] [[http://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] [[http://www.uniprot.org/uniprot/RL16_DEIRA RL16_DEIRA]] Binds the 5S and 23S rRNAs and is also seen to make contacts with the A and P site tRNAs. Interacts with A site tRNA mimics, and is probably one of the key factors, along with a helix of the 23S rRNA, in positioning tRNA stems in the peptidyl-transferase center.[HAMAP-Rule:MF_01342] [[http://www.uniprot.org/uniprot/RL24_DEIRA RL24_DEIRA]] One of two assembly initiator proteins, it binds directly to the 5'-end of the 23S rRNA, where it nucleates assembly of the 50S subunit (By similarity).[HAMAP-Rule:MF_01326_B] One of the proteins that surrounds the polypeptide exit tunnel on the outside of the subunit. Contacts trigger factor (TF) when it is bound to the ribosome; this contact may expose a hydrophobic crevice in TF (PubMed:16271892).[HAMAP-Rule:MF_01326_B] [[http://www.uniprot.org/uniprot/RL18_DEIRA RL18_DEIRA]] This is one of the proteins that binds and mediates the attachment of the 5S RNA into the large ribosomal subunit, where it forms part of the central protuberance.[HAMAP-Rule:MF_01337_B] [[http://www.uniprot.org/uniprot/RL19_DEIRA RL19_DEIRA]] This protein is located at the 30S-50S ribosomal subunit interface and may play a role in the structure and function of the aminoacyl-tRNA binding site (By similarity). Binds the 23S rRNA.[HAMAP-Rule:MF_00402] [[http://www.uniprot.org/uniprot/RL11_DEIRA RL11_DEIRA]] This protein binds directly to 23S ribosomal RNA and also contacts the CTC protein (RL25).[HAMAP-Rule:MF_00736_B] [[http://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] [[http://www.uniprot.org/uniprot/RL29_DEIRA RL29_DEIRA]] Binds the 23S rRNA. One of the proteins that surrounds the polypeptide exit tunnel on the outside of the subunit.[HAMAP-Rule:MF_00374] [[http://www.uniprot.org/uniprot/RL23_DEIRA RL23_DEIRA]] One of the early assembly protein (By similarity) it binds 23S rRNA. One of the proteins that surrounds the polypeptide exit tunnel on the outside of the subunit. Forms the main docking site for trigger factor binding to the ribosome (PubMed:16091460 and PubMed:16271892).[HAMAP-Rule:MF_01369] [[http://www.uniprot.org/uniprot/RL14_DEIRA RL14_DEIRA]] Forms part of two intersubunit bridges in the 70S ribosome (By similarity). Binds to 23S rRNA.[HAMAP-Rule:MF_01367] [[http://www.uniprot.org/uniprot/RL4_DEIRA RL4_DEIRA]] One of the primary rRNA binding proteins, this protein initially binds near the 5'-end of the 23S rRNA. It is important during the early stages of 50S assembly (By similarity).[HAMAP-Rule:MF_01328_B] Makes multiple contacts with different domains of the 23S rRNA in the assembled 50S subunit.[HAMAP-Rule:MF_01328_B] This protein is located close to the polypeptide exit tunnel, and interacts with the modified macrolide azithromycin, which blocks the tunnel.[HAMAP-Rule:MF_01328_B] | + | [https://www.uniprot.org/uniprot/RL2_DEIRA RL2_DEIRA] One of the primary rRNA binding proteins. Required for association of the 30S and 50S subunits to form the 70S ribosome, for tRNA binding and peptide bond formation. It has been suggested to have peptidyltransferase activity; this is somewhat controversial. Makes several contacts with the 16S rRNA in the 70S ribosome (By similarity).[HAMAP-Rule:MF_01320_B] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 22: |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Deinococcus radiodurans]] | + | [[Category: Deinococcus radiodurans R1]] |
| - | [[Category: Deinococcus radiodurans r1]]
| + | |
| - | [[Category: Deira]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Bashan, A]] | + | [[Category: Bashan A]] |
| - | [[Category: Eyal, Z]] | + | [[Category: Diskin Posner Y]] |
| - | [[Category: Krupkin, M]] | + | [[Category: Eyal Z]] |
| - | [[Category: Matzov, D]] | + | [[Category: Krupkin M]] |
| - | [[Category: Posner, Y Diskin]] | + | [[Category: Matzov D]] |
| - | [[Category: Rozenberg, H]] | + | [[Category: Rozenberg H]] |
| - | [[Category: Wekselman, I]] | + | [[Category: Wekselman I]] |
| - | [[Category: Yonath, A]] | + | [[Category: Yonath A]] |
| - | [[Category: Zimmerman, E]] | + | [[Category: Zimmerman E]] |
| - | [[Category: Avilamycin]]
| + | |
| - | [[Category: Degradable antibiotic]]
| + | |
| - | [[Category: Deinococcus radioduran]]
| + | |
| - | [[Category: Large ribosomal subunit]]
| + | |
| - | [[Category: Resistance]]
| + | |
| - | [[Category: Ribosome]]
| + | |
| Structural highlights
Function
RL2_DEIRA One of the primary rRNA binding proteins. Required for association of the 30S and 50S subunits to form the 70S ribosome, for tRNA binding and peptide bond formation. It has been suggested to have peptidyltransferase activity; this is somewhat controversial. Makes several contacts with the 16S rRNA in the 70S ribosome (By similarity).[HAMAP-Rule:MF_01320_B]
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Krupkin M, Wekselman I, Matzov D, Eyal Z, Diskin Posner Y, Rozenberg H, Zimmerman E, Bashan A, Yonath A. Avilamycin and evernimicin induce structural changes in rProteins uL16 and CTC that enhance the inhibition of A-site tRNA binding. Proc Natl Acad Sci U S A. 2016 Nov 1;113(44):E6796-E6805. Epub 2016 Oct 19. PMID:27791159 doi:http://dx.doi.org/10.1073/pnas.1614297113
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