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<p><i>Streptococcus pneumoniae</i> relies on sialic acid uptake for nutrition and human respiratory tract colonisation. The ATP binding cassette (ABC) transporter SatABC-MsmK facilitates this, with SatA being the substrate-binding protein (SBP). We show that SatA specifically recognises the α-anomer of N-acetylneuraminic acid (α-Neu5Ac). Crystallographic analysis, mutagenesis and binding affinity measurements identify conserved residues Phe87, Arg113, Gln216, Arg404 as critical for α-Neu5Ac coordination. Nuclear magnetic resonance spectroscopy confirms selective binding of α-Neu5Ac in buffered solution, despite its low equilibrium abundance. Isothermal titration calorimetry shows high affinity of SatA for the anomeric mixture of Neu5Ac (<i>K</i><sub>d</sub> ≈ 270 nM). The α-anomer preference of SatA, not previously observed in other SBPs, may confer selective advantage to <i>S. pneumoniae</i> by enabling uptake of α-Neu5Ac, the immediate product of sialidase-mediated glycan cleavage.</p><p></p>

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Streptococcus pneumoniae substrate binding protein SatA specifically recognises the α-anomer of N-acetylneuraminic acid

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月28日

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  • Misha Atkinson,
  • Claire M. Strain-Damerell,
  • Sridhar Sreeramulu,
  • Gemma Harris,
  • Charlotte L. Meller,
  • Tracey M. Gloster,
  • Frank Löhr,
  • Harald Schwalbe,
  • Petra Lukacik,
  • Martin A. Walsh

摘要

Streptococcus pneumoniae relies on sialic acid uptake for nutrition and human respiratory tract colonisation. The ATP binding cassette (ABC) transporter SatABC-MsmK facilitates this, with SatA being the substrate-binding protein (SBP). We show that SatA specifically recognises the α-anomer of N-acetylneuraminic acid (α-Neu5Ac). Crystallographic analysis, mutagenesis and binding affinity measurements identify conserved residues Phe87, Arg113, Gln216, Arg404 as critical for α-Neu5Ac coordination. Nuclear magnetic resonance spectroscopy confirms selective binding of α-Neu5Ac in buffered solution, despite its low equilibrium abundance. Isothermal titration calorimetry shows high affinity of SatA for the anomeric mixture of Neu5Ac (Kd ≈ 270 nM). The α-anomer preference of SatA, not previously observed in other SBPs, may confer selective advantage to S. pneumoniae by enabling uptake of α-Neu5Ac, the immediate product of sialidase-mediated glycan cleavage.