4v9s: Difference between revisions

Latest revision as of 23:07, 26 March 2025

Crystal structure of antibiotic GE82832 bound to 70S ribosome

Structural highlights

4v9s is a 20 chain structure with sequence from Thermus thermophilus HB8. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 3.1Å
Ligands:	004, 2QY, 2QZ, 2R1, 2R3, FME, K, MG, MVA, ZN
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

RS2_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 PubMed

The translocation of mRNA and tRNA through the ribosome is catalyzed by elongation factor G (EF-G), a universally conserved guanosine triphosphate hydrolase (GTPase). The mechanism by which the closely related decapeptide antibiotics dityromycin and GE82832 inhibit EF-G-catalyzed translocation is elucidated in this study. Using crystallographic and biochemical experiments, we demonstrate that these antibiotics bind to ribosomal protein S12 in solution alone as well as within the small ribosomal subunit, inducing long-range effects on the ribosomal head. The crystal structure of the antibiotic in complex with the 70S ribosome reveals that the binding involves conserved amino acid residues of S12 whose mutations result in in vitro and in vivo antibiotic resistance and loss of antibiotic binding. The data also suggest that GE82832/dityromycin inhibits EF-G-catalyzed translocation by disrupting a critical contact between EF-G and S12 that is required to stabilize the posttranslocational conformation of EF-G, thereby preventing the ribosome-EF-G complex from entering a conformation productive for translocation.

The antibiotics dityromycin and GE82832 bind protein S12 and block EF-G-catalyzed translocation.,Bulkley D, Brandi L, Polikanov YS, Fabbretti A, O'Connor M, Gualerzi CO, Steitz TA Cell Rep. 2014 Jan 30;6(2):357-65. doi: 10.1016/j.celrep.2013.12.024. Epub 2014, Jan 9. PMID:24412368^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Bulkley D, Brandi L, Polikanov YS, Fabbretti A, O'Connor M, Gualerzi CO, Steitz TA. The antibiotics dityromycin and GE82832 bind protein S12 and block EF-G-catalyzed translocation. Cell Rep. 2014 Jan 30;6(2):357-65. doi: 10.1016/j.celrep.2013.12.024. Epub 2014, Jan 9. PMID:24412368 doi:https://dx.doi.org/10.1016/j.celrep.2013.12.024

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OCA

[1] Bulkley D, Brandi L, Polikanov YS, Fabbretti A, O'Connor M, Gualerzi CO, Steitz TA. The antibiotics dityromycin and GE82832 bind protein S12 and block EF-G-catalyzed translocation. Cell Rep. 2014 Jan 30;6(2):357-65. doi: 10.1016/j.celrep.2013.12.024. Epub 2014, Jan 9. PMID:24412368 doi:https://dx.doi.org/10.1016/j.celrep.2013.12.024

[1]

@@ Line 3: / Line 3: @@
 <StructureSection load='4v9s' size='340' side='right'caption='[[4v9s]], [[Resolution|resolution]] 3.10&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4v9s]] 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=4nvy 4nvy], [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=4nvz 4nvz], [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=4nw0 4nw0] and [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=4nw1 4nw1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4V9S OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4V9S FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4v9s]] is a 20 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=4V9S OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4V9S FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=004:(2S)-AMINO(PHENYL)ETHANOIC+ACID'>004</scene>, <scene name='pdbligand=2QY:(2Z)-3-(4-HYDROXYPHENYL)-2-(METHYLAMINO)PROP-2-ENOIC+ACID'>2QY</scene>, <scene name='pdbligand=2QZ:N,N-DIMETHYL-L-THREONINE'>2QZ</scene>, <scene name='pdbligand=2R1:(2E)-2-AMINO-4-HYDROXY-3-[(2R)-OXIRAN-2-YL]BUT-2-ENOIC+ACID'>2R1</scene>, <scene name='pdbligand=2R3:(BETAR)-BETA-HYDROXY-O-METHYL-L-TYROSINE'>2R3</scene>, <scene name='pdbligand=FME:N-FORMYLMETHIONINE'>FME</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MVA:N-METHYLVALINE'>MVA</scene>, <scene name='pdbligand=SF4:IRON/SULFUR+CLUSTER'>SF4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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]] 3.1&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=004:(2S)-AMINO(PHENYL)ETHANOIC+ACID'>004</scene>, <scene name='pdbligand=2QY:(2Z)-3-(4-HYDROXYPHENYL)-2-(METHYLAMINO)PROP-2-ENOIC+ACID'>2QY</scene>, <scene name='pdbligand=2QZ:N,N-DIMETHYL-L-THREONINE'>2QZ</scene>, <scene name='pdbligand=2R1:(2E)-2-AMINO-4-HYDROXY-3-[(2R)-OXIRAN-2-YL]BUT-2-ENOIC+ACID'>2R1</scene>, <scene name='pdbligand=2R3:(BETAR)-BETA-HYDROXY-O-METHYL-L-TYROSINE'>2R3</scene>, <scene name='pdbligand=FME:N-FORMYLMETHIONINE'>FME</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MVA:N-METHYLVALINE'>MVA</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=4v9s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4v9s OCA], [https://pdbe.org/4v9s PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4v9s RCSB], [https://www.ebi.ac.uk/pdbsum/4v9s PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4v9s ProSAT]</span></td></tr>
 </table>
 == Function ==
-[https://www.uniprot.org/uniprot/RS4_THET8 RS4_THET8] One of the primary rRNA binding proteins, it binds directly to 16S rRNA where it helps nucleate assembly of the body and platform of the 30S subunit. Binds mRNA in the 70S ribosome, positioning it for translation.[HAMAP-Rule:MF_01306_B]
+[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 ==
@@ Line 20: / Line 21: @@
 ==See Also==
+*[[Ribosome 3D structures|Ribosome 3D structures]]
 *[[Transfer RNA (tRNA)|Transfer RNA (tRNA)]]
 == References ==

4v9s: Difference between revisions

Latest revision as of 23:07, 26 March 2025

Crystal structure of antibiotic GE82832 bound to 70S ribosome

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

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