6VLC

Crystal structure of UDP-GlcNAc 2-epimerase from Neisseria meningitidis bound to UDP-GlcNAc

Summary for 6VLC

• Entry DOI: 10.2210/pdb6vlc/pdb
• Related: 6VLB
• Descriptor: UDP-N-acetylglucosamine 2-epimerase, URIDINE-DIPHOSPHATE-N-ACETYLGLUCOSAMINE (3 entities in total)
• Functional Keywords: epimerase udp-glcnac udp-mannac udp-glcnac 2-epimerase, isomerase
• Biological source: Neisseria meningitidis Z2491
• Total number of polymer chains: 4
• Total formula weight: 172611.18

Authors

Fisher, A.J.,Hurlburt, N.K. (deposition date: 2020-01-23, release date: 2020-11-11, Last modification date: 2023-10-11)

Primary citation

Hurlburt, N.K.,Guan, J.,Ong, H.,Yu, H.,Chen, X.,Fisher, A.J.
Structural characterization of a nonhydrolyzing UDP-GlcNAc 2-epimerase from Neisseria meningitidis serogroup A.
Acta Crystallogr.,Sect.F, 76:557-567, 2020

PubMed Abstract: Bacterial nonhydrolyzing UDP-N-acetylglucosamine 2-epimerases catalyze the reversible interconversion of UDP-N-acetylglucosamine (UDP-GlcNAc) and UDP-N-acetylmannosamine (UDP-ManNAc). UDP-ManNAc is an important intermediate in the biosynthesis of certain cell-surface polysaccharides, including those in some pathogenic bacteria, such as Neisseria meningitidis and Streptococcus pneumoniae. Many of these epimerases are allosterically regulated by UDP-GlcNAc, which binds adjacent to the active site and is required to initiate UDP-ManNAc epimerization. Here, two crystal structures of UDP-N-acetylglucosamine 2-epimerase from Neisseria meningitidis serogroup A (NmSacA) are presented. One crystal structure is of the substrate-free enzyme, while the other structure contains UDP-GlcNAc substrate bound to the active site. Both structures form dimers as seen in similar epimerases, and substrate binding to the active site induces a large conformational change in which two Rossmann-like domains clamp down on the substrate. Unlike other epimerases, NmSacA does not require UDP-GlcNAc to instigate the epimerization of UDP-ManNAc, although UDP-GlcNAc was found to enhance the rate of epimerization. In spite of the conservation of residues involved in binding the allosteric UDP-GlcNAc observed in similar UDP-GlcNAc 2-epimerases, the structures presented here do not contain UDP-GlcNAc bound in the allosteric site. These structural results provide additional insight into the mechanism and regulation of this critical enzyme and improve the structural understanding of the ability of NmSacA to epimerize modified substrates.

PubMed: 33135674
DOI: 10.1107/S2053230X20013680

Experimental method

X-RAY DIFFRACTION (2.15 Å)