6EC8

Glutamylation domain, TbtB, from thiomuracin biosynthesis bound to 5'-phosphodesmethylglutamycin

6EC8 の概要

• エントリーDOI: 10.2210/pdb6ec8/pdb
• 分子名称: Lantibiotic dehydratase domain protein, 3'-deoxy-3'-[(L-alpha-glutamyl)amino]adenosine 5'-(dihydrogen phosphate) (3 entities in total)
• 機能のキーワード: ripp, thiopeptide, thiomuracin, trna-dependent, glutamylation, dehydratase, biosynthetic protein
• 由来する生物種: Thermobispora bispora (strain ATCC 19993 / DSM 43833 / CBS 139.67 / JCM 10125 / NBRC 14880 / R51)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 96482.19

構造登録者

Cogan, D.P.,Nair, S.K. (登録日: 2018-08-07, 公開日: 2019-06-19, 最終更新日: 2023-10-11)

主引用文献

Bothwell, I.R.,Cogan, D.P.,Kim, T.,Reinhardt, C.J.,van der Donk, W.A.,Nair, S.K.
Characterization of glutamyl-tRNA-dependent dehydratases using nonreactive substrate mimics.
Proc.Natl.Acad.Sci.USA, 116:17245-17250, 2019

PubMed Abstract: The peptide natural product nisin has been used as a food preservative for 6 decades with minimal development of resistance. Nisin contains the unusual amino acids dehydroalanine and dehydrobutyrine, which are posttranslationally installed by class I lanthipeptide dehydratases (LanBs) on a linear peptide substrate through an unusual glutamyl-tRNA-dependent dehydration of Ser and Thr. To date, little is known about how LanBs catalyze the transfer of glutamate from charged tRNA to the peptide substrate, or how they carry out the subsequent elimination of the peptide-glutamyl adducts to afford dehydro amino acids. Here, we describe the synthesis of inert analogs that mimic substrate glutamyl-tRNA and the glutamylated peptide intermediate, and determine the crystal structures of 2 LanBs in complex with each of these compounds. Mutational studies were used to characterize the function of the glutamylation and glutamate elimination active-site residues identified through the structural analysis. These combined studies provide insights into the mechanisms of substrate recognition, glutamylation, and glutamate elimination by LanBs to effect a net dehydration reaction of Ser and Thr.

PubMed: 31409709
DOI: 10.1073/pnas.1905240116

実験手法

X-RAY DIFFRACTION (2.148 Å)