Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	A binding site for the antibiotic GE81112 in the ribosomal mRNA channel.
Journal, issue, pages	bioRxiv, Year 2024
Publish date	Sep 26, 2024
Authors	Andreas Schedlbauer / Xu Han / Wouter van Bakel / Tatsuya Kaminishi / Borja Ochoa-Lizarralde / Idoia Iturrioz / Retina Çapuni / Ransford Parry / Ronny Zegarra / David Gil-Carton / Jorge P López-Alonso / Kristina Barragan Sanz / Letizia Brandi / Claudio O Gualerzi / Paola Fucini / Sean R Connell /
PubMed Abstract	The initiation phase is the rate-limiting step of protein synthesis (translation) and is finely regulated, making it an important drug target. In bacteria, initiation is guided by three initiation ...The initiation phase is the rate-limiting step of protein synthesis (translation) and is finely regulated, making it an important drug target. In bacteria, initiation is guided by three initiation factors and involves positioning the start site on the messenger RNA within the P-site on the small ribosomal subunit (30S), where it is decoded by the initiator tRNA. This process can be efficiently inhibited by GE81112, a natural hydrophilic, noncyclic, nonribosomal tetrapeptide. It is found in nature in three structural variants (A, B and B1 with molecular masses of 643-658 Da). Previous biochemical and structural characterisation of GE81112 indicates that the primary mechanism of action of this antibiotic is to (1) prevent the initiator tRNA from binding correctly to the P-site and (2) block conformational rearrangements in initiation factor IF3, resulting in an 30S pre/C state. In this study, using cryoEM, we have determined the binding site of GE81112 in initiation complexes (3.2-3.7Å) and on empty ribosomes (2.09 Å). This binding site is within the mRNA channel (E-site) but remote from the binding site of the initiation factors and initiator tRNA. This suggests that it acts allosterically to prevent the initiator tRNA from being locked into place. The binding mode is consistent with previous biochemical studies and recent work identifying the key pharmacophores of GE81112.
External links	bioRxiv / PubMed:39386670 / PubMed Central
Methods	EM (single particle)
Resolution	2.09 - 3.8 Å
Structure data	51936 9h8g EMDB-51936, PDB-9h8g: Complex 5 30S-GE81112 Method: EM (single particle) / Resolution: 2.09 Å 51964 9h9h EMDB-51964, PDB-9h9h: Complex 1 30S-IF1-IF2-IF3-GE81112 Method: EM (single particle) / Resolution: 3.8 Å 51965 9h9i EMDB-51965, PDB-9h9i: Complex 2 (HEAD) 30S-IF1-IF3-tRNA-GE81112 Method: EM (single particle) / Resolution: 3.2 Å 51966 9h9j EMDB-51966, PDB-9h9j: Complex 2 (BODY) 30S-IF1-IF3-tRNA-GE81112 Method: EM (single particle) / Resolution: 3.2 Å 51967 9h9k EMDB-51967, PDB-9h9k: Complex 3 (HEAD) 30S-tRNA-GE81112 Method: EM (single particle) / Resolution: 3.8 Å 51968 9h9l EMDB-51968, PDB-9h9l: Complex 3 (BODY) 30S-tRNA-GE81112 Method: EM (single particle) / Resolution: 3.2 Å 51969 9h9m EMDB-51969, PDB-9h9m: Complex 4 (HEAD) 30S-GE81112 (weak residual tRNA) Method: EM (single particle) / Resolution: 3.1 Å 51970 9h9n EMDB-51970, PDB-9h9n: Complex 4 (BODY) 30S-GE81112 (weak residual tRNA) Method: EM (single particle) / Resolution: 3.1 Å
Chemicals	PDB-1ic4: CRYSTAL STRUCTURE OF HYHEL-10 FV MUTANT(HD32A)-HEN LYSOZYME COMPLEX ChemComp-MG: Unknown entry ChemComp-K: Unknown entry ChemComp-HOH: WATER ChemComp-ZN: Unknown entry
Source	escherichia coli (E. coli)
Keywords	RIBOSOME / Antibiotic / initiation factor / GE81112 / 30S