Proteopedia

6dyn

C-terminal condensation domain of Ebony in complex with HistamineC-terminal condensation domain of Ebony in complex with Histamine

Structural highlights

6dyn 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 2.102Å
Ligands:,
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).[1] [2] [3] [4] [5] [6] [7] [8] [9] [10]

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[11]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

  1. ↑ Wittkopp PJ, True JR, Carroll SB. Reciprocal functions of the Drosophila yellow and ebony proteins in the development and evolution of pigment patterns. Development. 2002 Apr;129(8):1849-58. PMID:11934851 doi:10.1242/dev.129.8.1849
  2. ↑ Borycz J, Borycz JA, Loubani M, Meinertzhagen IA. tan and ebony genes regulate a novel pathway for transmitter metabolism at fly photoreceptor terminals. J Neurosci. 2002 Dec 15;22(24):10549-57. PMID:12486147 doi:10.1523/JNEUROSCI.22-24-10549.2002
  3. ↑ Richardt A, Kemme T, Wagner S, Schwarzer D, Marahiel MA, Hovemann BT. Ebony, a novel nonribosomal peptide synthetase for beta-alanine conjugation with biogenic amines in Drosophila. J Biol Chem. 2003 Oct 17;278(42):41160-6. PMID:12900414 doi:10.1074/jbc.M304303200
  4. ↑ Suh J, Jackson FR. Drosophila ebony activity is required in glia for the circadian regulation of locomotor activity. Neuron. 2007 Aug 2;55(3):435-47. PMID:17678856 doi:10.1016/j.neuron.2007.06.038
  5. ↑ Pérez MM, Schachter J, Berni J, Quesada-Allué LA. The enzyme NBAD-synthase plays diverse roles during the life cycle of Drosophila melanogaster. J Insect Physiol. 2010 Jan;56(1):8-13. PMID:19715698 doi:10.1016/j.jinsphys.2009.08.018
  6. ↑ Hartwig S, Dovengerds C, Herrmann C, Hovemann BT. Drosophila Ebony: a novel type of nonribosomal peptide synthetase related enzyme with unusually fast peptide bond formation kinetics. FEBS J. 2014 Nov;281(22):5147-58. PMID:25229196 doi:10.1111/febs.13054
  7. ↑ Izore T, Tailhades J, Hansen MH, Kaczmarski JA, Jackson CJ, Cryle MJ. Drosophila melanogaster nonribosomal peptide synthetase Ebony encodes an atypical condensation domain. Proc Natl Acad Sci U S A. 2019 Jan 31. pii: 1811194116. doi:, 10.1073/pnas.1811194116. PMID:30705105 doi:http://dx.doi.org/10.1073/pnas.1811194116
  8. ↑ Massey JH, Akiyama N, Bien T, Dreisewerd K, Wittkopp PJ, Yew JY, Takahashi A. Pleiotropic Effects of ebony and tan on Pigmentation and Cuticular Hydrocarbon Composition in Drosophila melanogaster. Front Physiol. 2019 May 1;10:518. PMID:31118901 doi:10.3389/fphys.2019.00518
  9. ↑ Hotta Y, Benzer S. Abnormal electroretinograms in visual mutants of Drosophila. Nature. 1969 Apr 26;222(5191):354-6. PMID:5782111 doi:10.1038/222354a0
  10. ↑ Walter MF, Zeineh LL, Black BC, McIvor WE, Wright TR, Biessmann H. Catecholamine metabolism and in vitro induction of premature cuticle melanization in wild type and pigmentation mutants of Drosophila melanogaster. Arch Insect Biochem Physiol. 1996;31(2):219-33. PMID:8580497 doi:<219::AID-ARCH9>3.0.CO;2-U 10.1002/(SICI)1520-6327(1996)31:2<219::AID-ARCH9>3.0.CO;2-U
  11. ↑ Izore T, Tailhades J, Hansen MH, Kaczmarski JA, Jackson CJ, Cryle MJ. Drosophila melanogaster nonribosomal peptide synthetase Ebony encodes an atypical condensation domain. Proc Natl Acad Sci U S A. 2019 Jan 31. pii: 1811194116. doi:, 10.1073/pnas.1811194116. PMID:30705105 doi:http://dx.doi.org/10.1073/pnas.1811194116

6dyn, resolution 2.10Å

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