6KV9
MoeE5 in complex with UDP-glucuronic acid and NAD
Summary for 6KV9
| Entry DOI | 10.2210/pdb6kv9/pdb |
| Descriptor | MoeE5, NICOTINAMIDE-ADENINE-DINUCLEOTIDE, URIDINE-5'-DIPHOSPHATE-GLUCURONIC ACID, ... (4 entities in total) |
| Functional Keywords | substrate, complex, antibiotic, epimerase, galacturonic acid, biosynthetic protein |
| Biological source | Streptomyces viridosporus ATCC 14672 |
| Total number of polymer chains | 1 |
| Total formula weight | 37787.85 |
| Authors | Ko, T.-P.,Liu, W.,Sun, H.,Liu, W.,Chen, C.-C.,Guo, R.-T. (deposition date: 2019-09-03, release date: 2019-11-13, Last modification date: 2023-11-22) |
| Primary citation | Sun, H.,Ko, T.P.,Liu, W.,Liu, W.,Zheng, Y.,Chen, C.C.,Guo, R.T. Structure of an antibiotic-synthesizing UDP-glucuronate 4-epimerase MoeE5 in complex with substrate. Biochem.Biophys.Res.Commun., 521:31-36, 2020 Cited by PubMed Abstract: The 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 1.48 Å and 1.66 Å 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. PubMed: 31653344DOI: 10.1016/j.bbrc.2019.10.035 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.48 Å) |
Structure validation
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