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Importance of Co‐operative Hydrogen Bonding in the Apramycin‐Ribosomal Decoding A‐Site Interaction
Author(s) -
Pirrone Michael G.,
Ande Chennaiah,
Haldimann Klara,
Hobbie Sven N.,
Vasella Andrea,
Böttger Erik C.,
Crich David
Publication year - 2023
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.202200486
Subject(s) - intramolecular force , hydrogen bond , vicinal , ribosomal rna , chemistry , ribosomal protein , protonation , stereochemistry , crystallography , ribosome , biochemistry , molecule , organic chemistry , ion , rna , gene
An intramolecular hydrogen bond between the protonated equatorial 7’‐methylamino group of apramycin and the vicinal axial 6’‐hydroxy group acidifies the 6’‐hydroxy group leading to a strong hydrogen bond to A1408 in the ribosomal drug binding pocket in the decoding A site of the small ribosomal subunit. In 6’‐epiapramycin, the trans‐nature of the 6’‐hydroxy group and the 7’‐methylamino group results in a much weaker intramolecular hydrogen bond, and a consequently weaker cooperative hydrogen bonding network with A1408, resulting overall in reduced inhibition of protein synthesis and antibacterial activity.