Structural highlights
Publication Abstract from PubMedWith new strains of Acinetobacter baumannii undergoing genomic analysis, it has been possible to define regions of genomic plasticity (RGPs), encoding specific adaptive elements. For a selected RGP from a community-derived isolate of A. baumannii, we outline sequences compatible with biosynthetic machinery of surface polysaccharides, specifically enzymes utilized in the dehydration and conversion of UDP-N-acetyl-D-glucosamine (UDP-D-GlcNAc). We have determined the crystal structure of one of these, the epimerase Ab-WbjB. This dehydratase belongs to the 'extended' short-chain dehydrogenase/reductase (SDR) family, related in fold to previously characterised enzymes CapE and FlaA1. Our 2.65A resolution structure of Ab-WbjB shows a hexamer, organised into a trimer of chain pairs, with coenzyme NADP+ occupying each chain. Specific active-site interactions between each coenzyme and a lysine quaternary group of a neighbouring chain interconnect adjacent dimers, so stabilising the hexameric form. We show UDP-GlcNAc to be a specific substrate for Ab-WbjB, with binding evident by ITC (Ka = 0.23 mumol-1). The sequence of Ab-WbjB shows variation from the consensus active-site motifs of many SDR enzymes, demonstrating a likely catalytic role for a specific threonine sidechain (as an alternative to tyrosine) in the canonical active site chemistry of these epimerases. Crystal structure of a UDP-GlcNAc epimerase for surface polysaccharide biosynthesis in Acinetobacter baumannii.,Shah BS, Ashwood HE, Harrop SJ, Farrugia DN, Paulsen IT, Mabbutt BC PLoS One. 2018 Jan 19;13(1):e0191610. doi: 10.1371/journal.pone.0191610., eCollection 2018. PMID:29352301[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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