4qnw
Crystal structure of EasA, an old yellow enzyme from Aspergillus fumigatus
Structural highlights
FunctionEASA_ASPFU Aldehyde reductase; part of the gene cluster that mediates the biosynthesis of fumiclavanine C, a fungal ergot alkaloid (PubMed:15933009, PubMed:22453123). DmaW catalyzes the first step of ergot alkaloid biosynthesis by condensing dimethylallyl diphosphate (DMAP) and tryptophan to form 4-dimethylallyl-L-tryptophan (PubMed:15870460). The second step is catalyzed by the methyltransferase easF that methylates 4-dimethylallyl-L-tryptophan in the presence of S-adenosyl-L-methionine, resulting in the formation of 4-dimethylallyl-L-abrine (By similarity). The catalase easC and the FAD-dependent oxidoreductase easE then transform 4-dimethylallyl-L-abrine to chanoclavine-I which is further oxidized by EasD in the presence of NAD(+), resulting in the formation of chanoclavine-I aldehyde (PubMed:20039019, PubMed:20526482, PubMed:21409592). EasA reduces chanoclavine-I aldehyde to dihydrochanoclavine-I aldehyde that spontaneously dehydrates to form 6,8-dimethyl-6,7-didehydroergoline (PubMed:20526482). EasG then catalyzes the reduction of 6,8-dimethyl-6,7-didehydroergoline to form festuclavine (PubMed:20526482). Hydrolysis of festuclavine by easM then leads to the formation of fumigaclavine B which is in turn acetylated by easN to fumigaclavine A (PubMed:26972831). Finally, easL catalyzes the conversion of fumigaclavine A into fumigaclavine C by attaching a dimethylallyl moiety to C-2 of the indole nucleus (PubMed:19672909).[UniProtKB:B6D5I7][1] [2] [3] [4] [5] [6] [7] [8] Publication Abstract from PubMedThe Aspergillus fumigatus old yellow enzyme (OYE) EasA reduces chanoclavine-I aldehyde to dihydrochanoclavine aldehyde and works in conjunction with festuclavine synthase at the branchpoint for ergot alkaloid pathways. The crystal structure of the FMN-loaded EasA was determined to 1.8 A resolution. The active-site amino acids of OYE are conserved, supporting a similar mechanism for reduction of the alpha/beta-unsaturated aldehyde. The C-terminal tail of one monomer packs into the active site of a monomer in the next asymmetric unit, which is most likely to be a crystallization artifact and not a mechanism of self-regulation. Structure of an Aspergillus fumigatus old yellow enzyme (EasA) involved in ergot alkaloid biosynthesis.,Chilton AS, Ellis AL, Lamb AL Acta Crystallogr F Struct Biol Commun. 2014 Oct 1;70(Pt 10):1328-32. doi:, 10.1107/S2053230X14018962. Epub 2014 Sep 25. PMID:25286934[9] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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