9J47

ScdA cysteine-free mutant from Staphylococcus aureus

Summary for 9J47

• Entry DOI: 10.2210/pdb9j47/pdb
• Descriptor: Iron-sulfur cluster repair protein ScdA, FE (III) ION, OXYGEN ATOM (3 entities in total)
• Functional Keywords: hemerythrin, oxygen binding
• Biological source: Staphylococcus aureus
• Total number of polymer chains: 2
• Total formula weight: 51094.86

Authors

Liao, W.Y.,Hu, N.J.,Chiang, Y.W. (deposition date: 2024-08-09, release date: 2025-08-13, Last modification date: 2025-09-17)

Primary citation

Chen, H.Y.,Tsai, R.F.,Lu, Y.S.,Cheng, Y.C.,Fan-Chiang, H.Y.,Wu, C.Y.,Lo, F.C.,Kuo, H.W.,Yang, W.K.,Liao, W.Y.,Hu, N.J.,Sue, S.C.,Chiang, Y.W.
Structure and Nitrite Reductase Activity of the Di-iron Protein ScdA in Staphylococcus aureus .
J.Am.Chem.Soc., 147:31558-31569, 2025

PubMed Abstract: Pathogenic endures bursts of host-derived reactive nitrogen species, yet the molecular defenses that enable this resilience have remained unclear. We now show that the previously enigmatic di-iron enzyme ScdA functions as a nitrite reductase, converting nitrite to nitric oxide (NO), and we elucidate the structural elements that support this activity. Using an integrative toolkit─X-ray crystallography, solution NMR, AlphaFold modeling, and pulsed EPR/DEER─we solved the full-length homodimeric structure of ScdA and identified a robust di-iron center that forms stable iron-nitrosyl intermediates. Targeted mutagenesis reveals that redox-active cysteines and dimerization state tune catalytic output, whereas steady-state kinetics confirm efficient nitrite-to-NO turnover. In vivo, ScdA overexpression in suppresses growth under nitrite-rich conditions, highlighting the cytotoxic potency of the NO it generates. By coupling structure to function, our work clarifies strategies for managing nitrosylative stress and points to ScdA as a potential vulnerability in antibiotic-resistant pathogens.

PubMed: 40846682
DOI: 10.1021/jacs.5c05573

Experimental method

X-RAY DIFFRACTION (2.38 Å)