Structural highlights
FunctionPublication Abstract from PubMedSialic 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 Acinetobacter baumannii 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 C2221 to P212121 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 Neisseria meningitidis) appear to be common in tetrameric organization. The revised two-base catalytic mechanism may involve His125 (Glu134 in GNE), as suggested by mutant activity analysis. The tetrameric structure of sialic-acid-synthesizing UDP-GlcNAc 2-epimerase from Acinetobacter baumannii: a comparative study with human GNE.,Ko TP, Lai SJ, Hsieh TJ, Yang CS, Chen Y J Biol Chem. 2018 May 15. pii: RA118.001971. doi: 10.1074/jbc.RA118.001971. PMID:29764940[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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