6DYN

C-terminal condensation domain of Ebony in complex with Histamine

Summary for 6DYN

• Entry DOI: 10.2210/pdb6dyn/pdb
• Descriptor: Ebony, HISTAMINE, CALCIUM ION, ... (4 entities in total)
• Functional Keywords: nrps, condensation domain, peptide-bond formation, biosynthetic protein
• Biological source: Drosophila melanogaster (Fruit fly)
• Total number of polymer chains: 1
• Total formula weight: 26142.73

Authors

Izore, T.,Tailhades, J.,Hansen, M.H.,Kaczmarski, J.A.,Jackson, C.J.,Cryle, M.J. (deposition date: 2018-07-02, release date: 2019-01-30, Last modification date: 2023-10-11)

Primary citation

Izore, T.,Tailhades, J.,Hansen, M.H.,Kaczmarski, J.A.,Jackson, C.J.,Cryle, M.J.
Drosophila melanogasternonribosomal peptide synthetase Ebony encodes an atypical condensation domain.
Proc. Natl. Acad. Sci. U.S.A., 116:2913-2918, 2019

PubMed Abstract: The protein Ebony from 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--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.

PubMed: 30705105
DOI: 10.1073/pnas.1811194116

Experimental method

X-RAY DIFFRACTION (2.102 Å)