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Cyclodipeptide Synthases of the NYH Subfamily Recognize tRNA Using an α-Helix Enriched with Positive Residues

Abstract : Cyclodipeptide synthases (CDPSs) perform nonribosomal protein synthesis using two aminoacyl-tRNA substrates to produce cyclodipeptides. There is no available structural detail on the CDPS:tRNA interaction to date. Using AlbC, a CDPS that produces cyclo(L-Phe-L-Phe), the interaction between AlbC with its Phe-tRNA substrate was investigated. Simulations of models of the AlbC:tRNA complex, proposed by rigid body docking or homology modeling, demonstrated that interactions with residues of an AlbC alpha helix, α4, significantly contribute to the binding free energy of AlbC to tRNA. Individual residue contributions to the tRNA binding free energy of the discovered binding mode explain well available biochemical data, and the results of in vivo assay experiments performed in this work and guided by simulations. In molecular dynamics simulations the phenylalanyl group predominantly occupied the two positions observed in the experimental structure of AlbC in the dipeptide intermediate state, suggesting that tRNAs of the first and second substrates interact with AlbC in a similar manner. Overall, given the high sequence and structural similarity among the members of the CDPS NYH protein subfamily, the mechanism of the protein:tRNA interaction is expected to be pertinent to a wide range of tRNA interacting proteins.
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Contributor : Alexey Aleksandrov <>
Submitted on : Wednesday, December 23, 2020 - 9:57:13 PM
Last modification on : Thursday, January 14, 2021 - 1:15:14 PM


Aleksandrov2020 Biochemistry.p...
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Anastasia Croitoru, Morgan Babin, Hannu Myllykallio, Muriel Gondry, Alexey Aleksandrov. Cyclodipeptide Synthases of the NYH Subfamily Recognize tRNA Using an α-Helix Enriched with Positive Residues. Biochemistry, American Chemical Society, 2021, 60 (1), pp.64-76. ⟨10.1021/acs.biochem.0c00761⟩. ⟨hal-03084339⟩



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