Structural highlights
FunctionPublication Abstract from PubMedThe sulfonamide-degrading monooxygenase sulX plays a dual role in bioremediation and antibiotic resistance, yet its molecular mechanism remains elusive. Here we report crystal structures of sulX in its ligand-free form, as an FMN-bound binary complex, and as ternary complexes with six distinct sulfonamides at resolutions ranging from 2.09 to 3.03â¯A. These structures reveal that sulfonamides bind on the re face of the flavin isoalloxazine ring, with their conserved 4-aminophenol and sulfonyl moieties tightly anchored by pi-stacking and hydrogen-bonding interactions, while the divergent aminated substituents extend into an open cleft with minimal specific contacts-a feature that explains the enzyme's remarkable capacity to accommodate diverse sulfonamide substrates. By integrating structural and biochemical data, we propose a catalytic mechanism involving F265-mediated substrate gating and H397-facilitated proton transfer. In addition, structure-based engineering yielded enhanced variants: A399S, which introduces new hydrogen bonds, showed a 37% increase in activity, and P422K achieved a 29% improvement. Our findings establish the structural basis of sulX-mediated sulfonamide degradation and provide a foundation for understanding sulfonamide resistance mechanisms. Structural insights into sulfonamide degradation by a two-component flavin-dependent monooxygenase.,Hu Y, Liu W, Zhang Q, Gao Z, Zhang H, Li H, Dai L J Hazard Mater. 2026 Sep 15;517:143643. doi: 10.1016/j.jhazmat.2026.143643. PMID:42748825[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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