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Staphylococcus aureus Growth using Human Hemoglobin as an Iron Source
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Structural basis for heme binding by the Shr protein from Streptococcus pyogenes

Kanta Seki1, Akinobu Senoo1, Satoru Nagatoishi2

  • 1Laboratory of Protein Drug Discovery, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.

The Journal of Biological Chemistry
|December 7, 2025
PubMed

Insights

This study reveals the crystal structures of key heme-binding domains in Streptococcus pyogenes, identifying methionine residues crucial for iron acquisition. These findings offer new targets for combating antibiotic-resistant bacterial infections.

Area of Science:

  • Microbiology
  • Structural Biology
  • Biochemistry

Background:

  • Streptococcus pyogenes is a significant pathogen causing various infections.
  • Increasing antibiotic resistance necessitates novel therapeutic strategies targeting bacterial virulence factors.
  • Iron acquisition is a critical virulence mechanism for S. pyogenes, utilizing the Shr protein to bind host hemoglobin.

Purpose of the Study:

  • To determine the crystal structures of the NEAr-Transporter (NEAT) domains within the Shr protein of S. pyogenes.
  • To elucidate the structural basis of heme binding by Shr's NEAT domains.
  • To identify potential therapeutic targets for S. pyogenes infections.

Main Methods:

  • X-ray crystallography was used to determine the structures of the Linker-NEAT1 and NEAT2 domains.
  • Structural analysis was performed to identify key residues involved in heme binding.
  • Site-directed mutagenesis was employed to validate the role of identified residues.

Main Results:

  • The crystal structures of Shr's Linker-NEAT1 and NEAT2 domains were determined at 2.35 Å and 2.66 Å resolution, respectively.
  • Structural and mutational analyses identified methionine residues as critical for heme binding in S. pyogenes Shr.
  • This methionine-dependent heme binding appears unique to S. pyogenes compared to other gram-positive species.

Conclusions:

  • The determined structures provide crucial insights into the heme acquisition mechanism of S. pyogenes.
  • Methionine residues are essential for heme binding in S. pyogenes Shr NEAT domains.
  • Understanding this pathway may lead to the development of new antimicrobial therapies against S. pyogenes.
Keywords:
NEAT domainShrsStreptococcus pyogenesX-ray crystallographyaxial coordinationhemeheme binding domainheme transfer

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