5XVS

Crystal structure of UDP-GlcNAc 2-epimerase NeuC complexed with UDP

Summary for 5XVS

• Entry DOI: 10.2210/pdb5xvs/pdb
• Related: 5H50 5H6P
• Descriptor: GDP/UDP-N,N'-diacetylbacillosamine 2-epimerase (Hydrolyzing), LITHIUM ION, URIDINE-5'-DIPHOSPHATE, ... (5 entities in total)
• Functional Keywords: neuc, udp n-acetylglucosamine 2-epimerase, transferase, hydrolase
• Biological source: Acinetobacter baumannii
• Total number of polymer chains: 2
• Total formula weight: 85644.24

Authors

Ko, T.P.,Hsieh, T.J.,Chen, S.C.,Wu, S.C.,Guan, H.H.,Yang, C.H.,Chen, C.J.,Chen, Y. (deposition date: 2017-06-28, release date: 2018-04-11, Last modification date: 2023-11-22)

Primary citation

Ko, T.P.,Lai, S.J.,Hsieh, T.J.,Yang, C.S.,Chen, Y.
The tetrameric structure of sialic acid-synthesizing UDP-GlcNAc 2-epimerase fromAcinetobacter baumannii: A comparative study with human GNE.
J. Biol. Chem., 293:10119-10127, 2018

PubMed Abstract: Sialic acid presentation on the cell surface by some pathogenic strains of bacteria allows their escape from the host immune system. It is one of the major virulence factors. Bacterial biosynthesis of sialic acids starts with the conversion of UDP-GlcNAc to UDP and ManNAc by a hydrolyzing 2-epimerase. Here, we present the crystal structure of this enzyme, named NeuC, from The protein folds into two Rossmann-like domains and forms dimers and tetramers as does the epimerase part of the bifunctional UDP-GlcNAc 2-epimerase/ManNAc kinase (GNE). In contrast to human GNE, which showed only the closed conformation, the NeuC crystals contained both open and closed protomers in each dimer. Substrate soaking changed the space group from C222 to P222 In addition to UDP, an intermediate-like ligand was seen bound to the closed protomer. The UDP-binding mode in NeuC was similar to that in GNE, although a few side chains were rotated away. NeuC lacks the CMP-Neu5Ac-binding site for allosteric inhibition of GNE. However, the two enzymes as well as other NeuC homologues (but not SiaA from ) appear to be common in tetrameric organization. The revised two-base catalytic mechanism may involve His-125 (Glu-134 in GNE), as suggested by mutant activity analysis.

PubMed: 29764940
DOI: 10.1074/jbc.RA118.001971

Experimental method

X-RAY DIFFRACTION (2.383 Å)