6RD1

Ruminococcus gnavus sialic acid aldolase catalytic lysine mutant in complex with sialic acid

Summary for 6RD1

• Entry DOI: 10.2210/pdb6rd1/pdb
• Related: 6RAB 6RB7
• Descriptor: Putative N-acetylneuraminate lyase, 5-(acetylamino)-3,5-dideoxy-D-glycero-D-galacto-non-2-ulosonic acid (3 entities in total)
• Functional Keywords: neu5ac, sialic acid, aldolase, lyase, ruminococcus gnavus
• Biological source: [Ruminococcus] gnavus ATCC 29149
• Total number of polymer chains: 2
• Total formula weight: 74825.65

Authors

Owen, C.D.,Bell, A.,Juge, N.,Walsh, M.A. (deposition date: 2019-04-12, release date: 2019-09-25, Last modification date: 2024-01-24)

Primary citation

Bell, A.,Brunt, J.,Crost, E.,Vaux, L.,Nepravishta, R.,Owen, C.D.,Latousakis, D.,Xiao, A.,Li, W.,Chen, X.,Walsh, M.A.,Claesen, J.,Angulo, J.,Thomas, G.H.,Juge, N.
Elucidation of a sialic acid metabolism pathway in mucus-foraging Ruminococcus gnavus unravels mechanisms of bacterial adaptation to the gut.
Nat Microbiol, 4:2393-2404, 2019

PubMed Abstract: Sialic acid (N-acetylneuraminic acid (Neu5Ac)) is commonly found in the terminal location of colonic mucin glycans where it is a much-coveted nutrient for gut bacteria, including Ruminococcus gnavus. R. gnavus is part of the healthy gut microbiota in humans, but it is disproportionately represented in diseases. There is therefore a need to understand the molecular mechanisms that underpin the adaptation of R. gnavus to the gut. Previous in vitro research has demonstrated that the mucin-glycan-foraging strategy of R. gnavus is strain dependent and is associated with the expression of an intramolecular trans-sialidase, which releases 2,7-anhydro-Neu5Ac, rather than Neu5Ac, from mucins. Here, we unravelled the metabolism pathway of 2,7-anhydro-Neu5Ac in R. gnavus that is underpinned by the exquisite specificity of the sialic transporter for 2,7-anhydro-Neu5Ac and by the action of an oxidoreductase that converts 2,7-anhydro-Neu5Ac into Neu5Ac, which then becomes a substrate of a Neu5Ac-specific aldolase. Having generated an R. gnavus nan-cluster deletion mutant that lost the ability to grow on sialylated substrates, we showed that-in gnotobiotic mice colonized with R. gnavus wild-type (WT) and mutant strains-the fitness of the nan mutant was significantly impaired, with a reduced ability to colonize the mucus layer. Overall, we revealed a unique sialic acid pathway in bacteria that has important implications for the spatial adaptation of mucin-foraging gut symbionts in health and disease.

PubMed: 31636419
DOI: 10.1038/s41564-019-0590-7

Experimental method

X-RAY DIFFRACTION (1.892 Å)