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- North, Rachel A, et al.
(författare)
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Structure and inhibition of N-acetylneuraminate lyase from methicillin-resistant Staphylococcus aureus
- 2016
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Ingår i: FEBS Letters. - : Wiley. - 0014-5793 .- 1873-3468. ; 590:23, s. 4414-4428
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Tidskriftsartikel (refereegranskat)abstract
- N-Acetylneuraminate lyase is the first committed enzyme in the degradation of sialic acid by bacterial pathogens. In this study, we analyzed the kinetic parameters of N-acetylneuraminate lyase from methicillin-resistant Staphylococcus aureus (MRSA). We determined that the enzyme has a relatively high KM of 3.2 mm, suggesting that flux through the catabolic pathway is likely to be controlled by this enzyme. Our data indicate that sialic acid alditol, a known inhibitor of N-acetylneuraminate lyase enzymes, is a stronger inhibitor of MRSA N-acetylneuraminate lyase than of Clostridium perfringens N-acetylneuraminate lyase. Our analysis of the crystal structure of ligand-free and 2R-sialic acid alditol-bound MRSA N-acetylneuraminate lyase suggests that subtle dynamic differences in solution and/or altered binding interactions within the active site may account for species-specific inhibition.
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2. |
- North, Rachel A, et al.
(författare)
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"Just a spoonful of sugar...": import of sialic acid across bacterial cell membranes
- 2018
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Ingår i: Biophysical reviews. - : Springer Science and Business Media LLC. - 1867-2450 .- 1867-2469. ; 10:2, s. 219-227
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Forskningsöversikt (refereegranskat)abstract
- Eukaryotic cell surfaces are decorated with a complex array of glycoconjugates that are usually capped with sialic acids, a large family of over 50 structurally distinct nine-carbon amino sugars, the most common member of which is N-acetylneuraminic acid. Once made available through the action of neuraminidases, bacterial pathogens and commensals utilise host-derived sialic acid by degrading it for energy or repurposing the sialic acid onto their own cell surface to camouflage the bacterium from the immune system. A functional sialic acid transporter has been shown to be essential for the uptake of sialic acid in a range of human bacterial pathogens and important for host colonisation and persistence. Here, we review the state-of-play in the field with respect to the molecular mechanisms by which these bio-nanomachines transport sialic acids across bacterial cell membranes.
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