Mycobacterium tuberculosis sulfurtransferase SseA is activated by its neighboring gene product Rv3284

Di Napoli, Giulia ; Fissore, Alex ; Salladini, Edoardo ; Raccuia, Eleonora ; Oliaro-Bosso, Simonetta ; Ruggiero, Alessia ; Berisio, Rita ; Medina, Milagros (Universidad de Zaragoza) ; Velazquez-Campoy, Adrian (Universidad de Zaragoza) ; Adinolfi, Salvatore ; Marengo, Mauro

Resumen: Tuberculosis remains a critical global health challenge, which underscores the need for new therapeutic targets. A potential drug target is the rhodanese‐like thiosulfate sulfurtransferase SseA, which plays a role in macrophage infection by Mycobacterium tuberculosis (Mtb) and its resistance to oxidative stress. In our research, we identified a protein (Rv3284), herein referred to as SufEMtb, that interacts with SseA and modulates its activity. Sequence analysis and molecular modeling revealed that SufEMtb enhances SseA enzymatic function by binding to its non‐catalytic N‐terminal domain and favoring an activating conformational change in a regulatory loop of SseA. This interaction appears crucial for effective enzyme activity and the maintenance of redox homeostasis in Mtb, making the SseA–SufEMtb complex a potential target for new therapies.

Idioma: Inglés

DOI: 10.1002/1873-3468.70117

Año: 2025

Publicado en: FEBS Letters 599, 16 (2025), 2362-2376
ISSN: 0014-5793

Financiación: info:eu-repo/grantAgreement/ES/DGA-FEDER/E35-23R
Financiación: info:eu-repo/grantAgreement/ES/MICINN/PID2022-136369NB-I00

Tipo y forma: Artículo (Versión definitiva)

Área (Departamento): Área Bioquímica y Biolog.Mole. (Dpto. Bioq.Biolog.Mol. Celular)