Structural highlights
Publication Abstract from PubMed
The tripeptide chains of the ergopeptines, a class of pharmacologically important D-lysergic acid alkaloid peptides, are arranged in a unique bicyclic cyclol based on an amino-terminal alpha-hydroxyamino acid and a terminal orthostructure. D-lysergyl-tripeptides are assembled by the nonribosomal peptide synthetases LPS1 and LPS2 of the ergot fungus Claviceps purpurea and released as N-(D-lysergyl-aminoacyl)-lactams. We show total enzymatic synthesis of ergopeptines catalyzed by a Fe2+/2-ketoglutarate-dependent dioxygenase (EasH) in conjunction with LPS1/LPS2. Analysis of the reaction indicated that EasH introduces a hydroxyl group into N-(D-lysergyl-aminoacyl)-lactam at alpha-C of the aminoacyl residue followed by spontaneous condensation with the terminal lactam carbonyl group. Sequence analysis revealed that EasH belongs to the wide and diverse family of the phytanoyl coenzyme A hydroxylases. We provide a high-resolution crystal structure of EasH that is most similar to that of phytanoyl coenzyme A hydroxylase, PhyH, from human.
Cyclolization of D-Lysergic Acid Alkaloid Peptides.,Havemann J, Vogel D, Loll B, Keller U Chem Biol. 2013 Dec 18. pii: S1074-5521(13)00417-1. doi:, 10.1016/j.chembiol.2013.11.008. PMID:24361048[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Havemann J, Vogel D, Loll B, Keller U. Cyclolization of D-Lysergic Acid Alkaloid Peptides. Chem Biol. 2013 Dec 18. pii: S1074-5521(13)00417-1. doi:, 10.1016/j.chembiol.2013.11.008. PMID:24361048 doi:http://dx.doi.org/10.1016/j.chembiol.2013.11.008
