Structural highlights
FunctionPublication Abstract from PubMedThe epimerase MoeE5 from Streptomyces viridosporus converts UDP-glucuronic acid (UDP-GlcA) to UDP-galacturonic acid (UDP-GalA) to provide the first sugar in synthesizing moenomycin, a potent inhibitor against bacterial peptidoglycan glycosyltransferases. The enzyme belongs to the UDP-hexose 4-epimerase family, and uses NAD(+) as its cofactor. Here we present the complex crystal structures of MoeE5/NAD(+)/UDP-GlcA and MoeE5/NAD(+)/UDP-glucose, determined at 1.48A and 1.66A resolution. The cofactor NAD(+) is bound to the N-terminal Rossmann-fold domain and the substrate is bound to the smaller C-terminal domain. In both crystals the C4 atom of the sugar moiety of the substrate is in close proximity to the C4 atom of the nicotinamide of NAD(+), and the O4 atom of the sugar is also hydrogen bonded to the side chain of Tyr154, suggesting a productive binding mode. As the first complex structure of this protein family with a bound UDP-GlcA in the active site, it shows an extensive hydrogen-bond network between the enzyme and the substrate. We further built a model with the product UDP-GalA, and found that the unique Arg192 of MoeE5 might play an important role in the catalytic pathway. Consequently, MoeE5 is likely a specific epimerase for UDP-GlcA to UDP-GalA conversion, rather than a promiscuous enzyme as some other family members. Structure of an antibiotic-synthesizing UDP-glucuronate 4-epimerase MoeE5 in complex with substrate.,Sun H, Ko TP, Liu W, Liu W, Zheng Y, Chen CC, Guo RT Biochem Biophys Res Commun. 2019 Oct 22. pii: S0006-291X(19)31924-2. doi:, 10.1016/j.bbrc.2019.10.035. PMID:31653344[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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