Unknown

Dataset Information

0

Drosophila melanogaster nonribosomal peptide synthetase Ebony encodes an atypical condensation domain.


ABSTRACT: The protein Ebony from Drosophila melanogaster plays a central role in the regulation of histamine and dopamine in various tissues through condensation of these amines with ?-alanine. Ebony is a rare example of a nonribosomal peptide synthetase (NRPS) from a higher eukaryote and contains a C-terminal sequence that does not correspond to any previously characterized NRPS domain. We have structurally characterized this C-terminal domain and have discovered that it adopts the aryl-alkylamine-N-acetyl transferase (AANAT) fold, which is unprecedented in NRPS biology. Through analysis of ligand-bound structures, activity assays, and binding measurements, we have determined how this atypical condensation domain is able to provide selectivity for both the carrier protein-bound amino acid and the amine substrates, a situation that remains unclear for standard condensation domains identified to date from NRPS assembly lines. These results demonstrate that the C terminus of Ebony encodes a eukaryotic example of an alternative type of NRPS condensation domain; they also illustrate how the catalytic components of such assembly lines are significantly more diverse than a minimal set of conserved functional domains.

SUBMITTER: Izore T 

PROVIDER: S-EPMC6386674 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

altmetric image

Publications

<i>Drosophila melanogaster</i> nonribosomal peptide synthetase Ebony encodes an atypical condensation domain.

Izoré Thierry T   Tailhades Julien J   Hansen Mathias Henning MH   Kaczmarski Joe A JA   Jackson Colin J CJ   Cryle Max J MJ  

Proceedings of the National Academy of Sciences of the United States of America 20190131 8


The protein Ebony from <i>Drosophila melanogaster</i> plays a central role in the regulation of histamine and dopamine in various tissues through condensation of these amines with β-alanine. Ebony is a rare example of a nonribosomal peptide synthetase (NRPS) from a higher eukaryote and contains a C-terminal sequence that does not correspond to any previously characterized NRPS domain. We have structurally characterized this C-terminal domain and have discovered that it adopts the aryl-alkylamine  ...[more]

Similar Datasets

| S-EPMC8244413 | biostudies-literature
| S-EPMC4351081 | biostudies-literature
| S-EPMC4318696 | biostudies-literature
| S-EPMC10029145 | biostudies-literature
| S-EPMC8807600 | biostudies-literature
| S-EPMC2034628 | biostudies-literature
| S-EPMC7450107 | biostudies-literature
| S-EPMC7163397 | biostudies-literature
| S-EPMC5551671 | biostudies-literature