Cyclolization of D-lysergic acid alkaloid peptides.
Chem Biol
; 21(1): 146-55, 2014 Jan 16.
Article
en En
| MEDLINE
| ID: mdl-24361048
ABSTRACT
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 α-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 Fe²âº/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 α-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.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Péptidos
/
Dioxigenasas
/
Ergotamina
/
Ácido Lisérgico
Idioma:
En
Revista:
Chem Biol
Asunto de la revista:
BIOLOGIA
/
BIOQUIMICA
/
QUIMICA
Año:
2014
Tipo del documento:
Article