9b00: Difference between revisions
New page: '''Unreleased structure''' The entry 9b00 is ON HOLD Authors: Batool, Z., Pavlova, J.A., Paranjpe, M.N., Tereshchenkov, A.G., Lukianov, D.A., Osterman, I.A., Bogdanov, A.A., Sumbatyan, ... |
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==Crystal structure of the wild-type Thermus thermophilus 70S ribosome in complex with berberine analog of chloramphenicol CAM-BER, mRNA, deacylated A- and E-site tRNAphe, and deacylated P-site tRNAmet at 2.80A resolution== | |||
<StructureSection load='9b00' size='340' side='right'caption='[[9b00]], [[Resolution|resolution]] 2.80Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[9b00]] 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=9B00 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9B00 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]] 2.8Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0TD:(3S)-3-(METHYLSULFANYL)-L-ASPARTIC+ACID'>0TD</scene>, <scene name='pdbligand=2MA:2-METHYLADENOSINE-5-MONOPHOSPHATE'>2MA</scene>, <scene name='pdbligand=2MG:2N-METHYLGUANOSINE-5-MONOPHOSPHATE'>2MG</scene>, <scene name='pdbligand=4OC:4N,O2-METHYLCYTIDINE-5-MONOPHOSPHATE'>4OC</scene>, <scene name='pdbligand=4SU:4-THIOURIDINE-5-MONOPHOSPHATE'>4SU</scene>, <scene name='pdbligand=5MC:5-METHYLCYTIDINE-5-MONOPHOSPHATE'>5MC</scene>, <scene name='pdbligand=5MU:5-METHYLURIDINE+5-MONOPHOSPHATE'>5MU</scene>, <scene name='pdbligand=A1AIX:13-(2-{[(1R,2R)-1,3-dihydroxy-1-(4-nitrophenyl)propan-2-yl]amino}-2-oxoethyl)-9,10-dimethoxy-5,6-dihydro-2H-[1,3]dioxolo[4,5-g]isoquinolino[3,2-a]isoquinolin-7-ium'>A1AIX</scene>, <scene name='pdbligand=G7M:N7-METHYL-GUANOSINE-5-MONOPHOSPHATE'>G7M</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=M2G:N2-DIMETHYLGUANOSINE-5-MONOPHOSPHATE'>M2G</scene>, <scene name='pdbligand=MA6:6N-DIMETHYLADENOSINE-5-MONOPHOSHATE'>MA6</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MIA:2-METHYLTHIO-N6-ISOPENTENYL-ADENOSINE-5-MONOPHOSPHATE'>MIA</scene>, <scene name='pdbligand=OMC:O2-METHYLYCYTIDINE-5-MONOPHOSPHATE'>OMC</scene>, <scene name='pdbligand=OMG:O2-METHYLGUANOSINE-5-MONOPHOSPHATE'>OMG</scene>, <scene name='pdbligand=OMU:O2-METHYLURIDINE+5-MONOPHOSPHATE'>OMU</scene>, <scene name='pdbligand=PSU:PSEUDOURIDINE-5-MONOPHOSPHATE'>PSU</scene>, <scene name='pdbligand=SF4:IRON/SULFUR+CLUSTER'>SF4</scene>, <scene name='pdbligand=UR3:3-METHYLURIDINE-5-MONOPHOSHATE'>UR3</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=9b00 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9b00 OCA], [https://pdbe.org/9b00 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9b00 RCSB], [https://www.ebi.ac.uk/pdbsum/9b00 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9b00 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/RL3_THET8 RL3_THET8] 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] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Chloramphenicol (CHL) is an antibiotic targeting the peptidyl transferase center in bacterial ribosomes. We synthesized a new analog, CAM-BER, by substituting the dichloroacetyl moiety of CHL with a positively charged aromatic berberine group. CAM-BER suppresses bacterial cell growth, inhibits protein synthesis in vitro, and binds tightly to the 70S ribosome. Crystal structure analysis reveals that the bulky berberine group folds into the P site of the peptidyl transferase center (PTC), where it competes with the formyl-methionine residue of the initiator tRNA. Our toe-printing data confirm that CAM-BER acts as a translation initiation inhibitor in stark contrast to CHL, a translation elongation inhibitor. Moreover, CAM-BER induces a distinct rearrangement of conformationally restrained nucleotide A2059, suggesting that the 23S rRNA plasticity is significantly higher than previously thought. CAM-BER shows potential in avoiding CHL resistance and presents opportunities for developing novel berberine derivatives of CHL through medicinal chemistry exploration. | |||
Berberine analog of chloramphenicol exhibits a distinct mode of action and unveils ribosome plasticity.,Batool Z, Pavlova JA, Paranjpe MN, Tereshchenkov AG, Lukianov DA, Osterman IA, Bogdanov AA, Sumbatyan NV, Polikanov YS Structure. 2024 Jul 6:S0969-2126(24)00231-4. doi: 10.1016/j.str.2024.06.013. PMID:39019034<ref>PMID:39019034</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 9b00" style="background-color:#fffaf0;"></div> | ||
[[Category: | == References == | ||
[[Category: | <references/> | ||
[[Category: | __TOC__ | ||
[[Category: | </StructureSection> | ||
[[Category: Pavlova | [[Category: Large Structures]] | ||
[[Category: | [[Category: Thermus thermophilus HB8]] | ||
[[Category: Sumbatyan | [[Category: Batool Z]] | ||
[[Category: Tereshchenkov | [[Category: Bogdanov AA]] | ||
[[Category: Lukianov DA]] | |||
[[Category: Osterman IA]] | |||
[[Category: Paranjpe MN]] | |||
[[Category: Pavlova JA]] | |||
[[Category: Polikanov YS]] | |||
[[Category: Sumbatyan NV]] | |||
[[Category: Tereshchenkov AG]] | |||