5tpr
Desmethyl-4-deoxygadusol synthase from Anabaena variabilis (Ava_3858) with NAD+ and Zn2+ bound
Structural highlights
FunctionDDGS_TRIV2 Catalyzes the conversion of sedoheptulose 7-phosphate to demethyl-4-deoxygadusol (DDG) (PubMed:22741921). Involved in the synthesis of the mycosporine-like amino acid shinorine, a natural sunscreen compound that protects the cell against UV radiation (By similarity).[UniProtKB:B2J6X9][1] Publication Abstract from PubMed2-Epi-5-epi-valiolone synthase (EEVS), a C7-sugar phosphate cyclase (SPC) homologous to 3-dehydroquinate synthase (DHQS), was discovered during studies of the biosynthesis of the C7N-aminocyclitol family of natural products. EEVS was originally thought to be present only in certain actinomycetes, but analyses of genome sequences showed that it is broadly distributed in both prokaryotes and eukaryotes, including vertebrates. Another SPC, desmethyl-4-deoxygadusol synthase (DDGS), was later discovered as being involved in the biosynthesis of mycosporine-like amino acid sunscreen compounds. Current database annotations are quite unreliable, with many EEVSs reported as DHQS, and most DDGSs reported as EEVS, DHQS, or simply hypothetical proteins. Here, we identify sequence features useful for distinguishing these enzymes, report a crystal structure of a representative DDGS showing the high similarity of the EEVS and DDGS enzymes, identify notable active site differences, and demonstrate the importance of two of these active site residues for catalysis by point mutations. Further, we functionally characterized two representatives of a distinct clade equidistant from known EEVS and known DDGS groups and show them to be authentic EEVSs. Moreover, we document and discuss the distribution of genes that encode EEVS and DDGS in various prokaryotes and eukaryotes, including pathogenic bacteria, plant symbionts, nitrogen-fixing bacteria, myxobacteria, cyanobacteria, fungi, stramenopiles, and animals, suggesting their broad potential biological roles in nature. Evolution and Distribution of C7-Cyclitol Synthases in Prokaryotes and Eukaryotes.,Osborn AR, Kean KM, Alseud KM, Almabruk KH, Asamizu S, Lee JA, Karplus PA, Mahmud T ACS Chem Biol. 2017 Feb 17. doi: 10.1021/acschembio.7b00066. PMID:28182402[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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