Scientific Reports (Apr 2024)

Catalytic specificity and crystal structure of cystathionine γ-lyase from Pseudomonas aeruginosa

  • Marco Pedretti,
  • Carmen Fernández-Rodríguez,
  • Carolina Conter,
  • Iker Oyenarte,
  • Filippo Favretto,
  • Adele di Matteo,
  • Paola Dominici,
  • Maria Petrosino,
  • Maria Luz Martinez-Chantar,
  • Tomas Majtan,
  • Alessandra Astegno,
  • Luis Alfonso Martínez-Cruz

DOI
https://doi.org/10.1038/s41598-024-57625-7
Journal volume & issue
Vol. 14, no. 1
pp. 1 – 14

Abstract

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Abstract The escalating drug resistance among microorganisms underscores the urgent need for innovative therapeutic strategies and a comprehensive understanding of bacteria's defense mechanisms against oxidative stress and antibiotics. Among the recently discovered barriers, the endogenous production of hydrogen sulfide (H2S) via the reverse transsulfuration pathway, emerges as a noteworthy factor. In this study, we have explored the catalytic capabilities and crystal structure of cystathionine γ-lyase from Pseudomonas aeruginosa (PaCGL), a multidrug-opportunistic pathogen chiefly responsible for nosocomial infections. In addition to a canonical l-cystathionine hydrolysis, PaCGL efficiently catalyzes the production of H2S using l-cysteine and/or l-homocysteine as alternative substrates. Comparative analysis with the human enzyme and counterparts from other pathogens revealed distinct structural features within the primary enzyme cavities. Specifically, a distinctly folded entrance loop could potentially modulate the access of substrates and/or inhibitors to the catalytic site. Our findings offer significant insights into the structural evolution of CGL enzymes across different pathogens and provide novel opportunities for developing specific inhibitors targeting PaCGL.

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