9XUB

Crystal Structure of Thioredoxin reductase from Mycobacterium tuberculosis.

Summary for 9XUB

• Entry DOI: 10.2210/pdb9xub/pdb
• Descriptor: Thioredoxin reductase, FLAVIN-ADENINE DINUCLEOTIDE (3 entities in total)
• Functional Keywords: thioredoxin reductase, mycobacterium tuberculosis, oxidoreductase
• Biological source: Mycobacterium tuberculosis (strain CDC 1551 / Oshkosh)
• Total number of polymer chains: 4
• Total formula weight: 134753.90

Authors

Li, Z.Y.,Niu, W.C.,Gong, Y.,Xu, Y.C.,Cao, P. (deposition date: 2025-11-24, release date: 2026-02-04, Last modification date: 2026-02-25)

Primary citation

Li, Z.,Niu, W.,Xia, D.,Chen, Y.,Chen, S.,Zhang, B.,Wang, J.,Zhu, H.,Yang, H.,Xie, F.,Zhou, Y.,Gong, Y.,Xu, Y.,Cao, P.
Structural and Mechanistic Characterization of Mycobacterium tuberculosis TrxR Inhibition by Glutathione-Coated Gold Nanocluster.
Int J Mol Sci, 27:-, 2026

PubMed Abstract: () relies on the thioredoxin (Trx)-thioredoxin reductase (TrxR) system to maintain intracellular redox homeostasis and to support Trx-dependent DNA synthesis and repair, making TrxR a potential target for anti-tuberculosis therapy. Gold nanoclusters have been reported to inhibit human TrxR and suppress tumor growth, suggesting that gold-based nanomaterials can modulate TrxR activity. In this study, we report a previously uncharacterized oxidized crystal structure of TrxR containing two dimers in the asymmetric unit and use this structure to investigate inhibition by a glutathione-coated gold nanocluster (GSH-AuNC). Biolayer interferometry and enzymatic assays show that GSH-AuNC binds directly to TrxR and efficiently inhibits its catalytic activity at the purified enzyme level. Molecular dynamics simulations indicate that GSH-AuNC can occupy a surface pocket proximal to the active site, providing a plausible structural basis for enzyme engagement. AlphaFold3 modeling of the TrxR-Trx heterodimeric complex defines the interaction interface required for productive electron transfer and provides a structural hypothesis for how GSH-AuNC disrupts this process. Together, these results provide structural and mechanistic insights into the biochemical modulation of TrxR by GSH-AuNC, while the antimycobacterial activity of GSH-AuNC remains to be evaluated in future studies.

PubMed: 41683636
DOI: 10.3390/ijms27031209

Experimental method

X-RAY DIFFRACTION (2.6 Å)