6dys | pdb_00006dys

C-terminal condensation domain of Ebony in complex with beta-alanyl-dopamine

spinqualitylabelsall models 6dys, resolution 2.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6dys is a 1 chain structure with sequence from Drosophila melanogaster. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.3Å Ligands: CA, HJ1 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function EBO_DROME Nonribosomal peptide synthase which is required for the regulation of histamine and dopamine levels in various tissues through their condensation with beta-alanine (PubMed:12900414, PubMed:19715698, PubMed:25229196, PubMed:30705105). In epithelial glial cells, plays an essential role in the inactivation of histamine, the main neurotransmitter in the optical nerve system, by catalyzing the conversion of histamine into carcinine (PubMed:5782111, PubMed:12486147, PubMed:12900414, PubMed:25229196, PubMed:30705105). In the cuticle, catalyzes the condensation of beta-alanine with dopamine to form beta-alanyl-dopamine (NBAD), a metabolite involved in the pigmentation and sclerotization of the insect cuticle (PubMed:8580497, PubMed:11934851). Also, regulates the cuticular hydrocarbon composition in females (PubMed:31118901). Acts downstream of the body clock to regulate circadian behavioral rhythms (PubMed:17678856). Can also condense beta-alanine with biogenic amines tyramine, octopamine, and serotonin in vitro (PubMed:12900414, PubMed:19715698). Publication Abstract from PubMed 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 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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