4f96 | pdb_00004f96
Crystal Structure of VldE, the pseudo-glycosyltransferase, in complex with GDP
Structural highlights
FunctionVLDE_STRHL Involved in the biosynthesis of the antifungal agent validamycin A (PubMed:16725283). Catalyzes the condensation between GDP-valienol and validamine 7-phosphate via a nonglycosidic C-N bond formation to yield validoxylamine A 7'-phosphate (PubMed:21766819).[1] [2] Publication Abstract from PubMedThe pseudo-glycosyltransferase VldE catalyzes non-glycosidic C-N coupling between an unsaturated cyclitol and a saturated aminocyclitol with the conservation of the stereochemical configuration of the substrates to form validoxylamine A 7'-phosphate, the biosynthetic precursor of the antibiotic validamycin A. To study the molecular basis of its mechanism, the three-dimensional structures of VldE from Streptomyces hygroscopicus subsp. limoneus was determined in apo form, in complex with GDP, in complex with GDP and validoxylamine A 7'-phosphate, and in complex with GDP and trehalose. The structure of VldE with the catalytic site in both an "open" and "closed" conformation is also described. With these structures, the preferred binding of the guanine moiety by VldE, rather than the uracil moiety as seen in OtsA could be explained. The elucidation of the VldE structure in complex with the entirety of its products provides insight into the internal return mechanism by which catalysis occurs with a net retention of the stereochemical configuration of the donated cyclitol. Mechanistic Insights into Validoxylamine A 7'-Phosphate Synthesis by VldE Using the Structure of the Entire Product Complex.,Cavalier MC, Yim YS, Asamizu S, Neau D, Almabruk KH, Mahmud T, Lee YH PLoS One. 2012;7(9):e44934. doi: 10.1371/journal.pone.0044934. Epub 2012 Sep 13. PMID:23028689[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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