6dyn
C-terminal condensation domain of Ebony in complex with HistamineC-terminal condensation domain of Ebony in complex with Histamine
Structural highlights
Publication Abstract from PubMedThe 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 beta-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. Drosophila melanogaster nonribosomal peptide synthetase Ebony encodes an atypical condensation domain.,Izore T, Tailhades J, Hansen MH, Kaczmarski JA, Jackson CJ, Cryle MJ Proc Natl Acad Sci U S A. 2019 Jan 31. pii: 1811194116. doi:, 10.1073/pnas.1811194116. PMID:30705105[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
|
| ||||||||||||||||