Structural insight into interaction between C20 phenylalanyl derivative of tylosin and ribosomal tunnel
- Authors: Makarov G.I.1,2, Sumbatyan N.V.2, Bogdanov A.A.1,3
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Affiliations:
- Faculty of Chemistry
- South Ural State University
- Belozersky Institute of Physico-Chemical Biology
- Issue: Vol 82, No 8 (2017)
- Pages: 925-932
- Section: Article
- URL: https://journals.rcsi.science/0006-2979/article/view/151451
- DOI: https://doi.org/10.1134/S0006297917080077
- ID: 151451
Cite item
Abstract
Macrolides are clinically important antibiotics that inhibit protein biosynthesis on ribosomes by binding to ribosomal tunnel. Tylosin belongs to the group of 16-membered macrolides. It is a potent inhibitor of translation whose activity is largely due to reversible covalent binding of its aldehyde group with the base of A2062 in 23S ribosomal RNA. It is known that the conversion of the aldehyde group of tylosin to methyl or carbinol groups dramatically reduces its inhibitory activity. However, earlier we obtained several derivatives of tylosin having comparable activity in spite of the fact that the aldehyde group of tylosin in these compounds was substituted with an amino acid or a peptide residue. Details of the interaction of these compounds with the ribosome that underlies their high inhibitory activity were not known. In the present work, the structure of the complex of tylosin derivative containing in position 20 the residue of ethyl ester of 2-imino(oxy)acetylphenylalanine with the tunnel of the E. coli ribosome was identified by means of molecular dynamics simulations, which could explain high biological activity of this compound.
Keywords
About the authors
G. I. Makarov
Faculty of Chemistry; South Ural State University
Email: bogdanov@belozersky.msu.ru
Russian Federation, Moscow, 119991; Chelyabinsk, 454080
N. V. Sumbatyan
South Ural State University
Email: bogdanov@belozersky.msu.ru
Russian Federation, Chelyabinsk, 454080
A. A. Bogdanov
Faculty of Chemistry; Belozersky Institute of Physico-Chemical Biology
Author for correspondence.
Email: bogdanov@belozersky.msu.ru
Russian Federation, Moscow, 119991; Moscow, 119992