Current Research in Structural Biology (Jan 2024)

Structural and functional insights of sortases and their interactions with antivirulence compounds

  • Sowmiya Sri Sivaramalingam,
  • Deepsikha Jothivel,
  • Deenadayalan Karaiyagowder Govindarajan,
  • Lohita Kadirvelu,
  • Muthusaravanan Sivaramakrishnan,
  • Dhivia Dharshika Chithiraiselvan,
  • Kumaravel Kandaswamy

Journal volume & issue
Vol. 8
p. 100152

Abstract

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Sortase proteins play a crucial role as integral membrane proteins in anchoring bacterial surface proteins by recognizing them through a Cell-Wall Sorting (CWS) motif and cleaving them at specific sites before initiating pilus assembly. Both sortases and their substrate proteins are major virulence factors in numerous Gram-positive pathogens, making them attractive targets for antimicrobial intervention. Recognizing the significance of virulence proteins, a comprehensive exploration of their structural and functional characteristics is essential to enhance our understanding of pilus assembly in diverse Gram-positive bacteria. Therefore, this review article discusses the structural features of different classes of sortases and pilin proteins, primarily serving as substrates for sortase-assembled pili. Moreover, it thoroughly examines the molecular-level interactions between sortases and their inhibitors, providing insights from both structural and functional perspectives. In essence, this review article will provide a contemporary and complete understanding of both sortase pathways and various strategies to target them effectively to counteract the virulence.

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