9EGH

Crystal Structure of EgtUC binding domain mutant I243A bound to L-Ergothioneine from S. pneumoniae

Summary for 9EGH

• Entry DOI: 10.2210/pdb9egh/pdb
• Descriptor: Ergothioneine transporter EgtUC, trimethyl-[(2S)-1-oxidanyl-1-oxidanylidene-3-(2-sulfanylidene-1,3-dihydroimidazol-4-yl)propan-2-yl]azanium (3 entities in total)
• Functional Keywords: l-ergothioneine, abc transporter, s. pneumoniae, transport protein
• Biological source: Streptococcus pneumoniae D39
• Total number of polymer chains: 2
• Total formula weight: 62513.16

Authors

Legg, K.A.,Gonzalez-Gutierrez, G.,Giedroc, D.P. (deposition date: 2024-11-21, release date: 2025-11-26, Last modification date: 2026-04-15)

Primary citation

Legg, K.A.,Gonzalez-Gutierrez, G.,Edmonds, K.A.,Shushkov, P.G.,Giedroc, D.P.
CH•••S hydrogen bonds drive molecular recognition of ergothioneine by the microbial transporter.
Sci Adv, 12:eaeb0426-eaeb0426, 2026

PubMed Abstract: Many bacteria harbor an ATP-binding cassette (ABC) transporter named EgtU specific for the human dietary antioxidant and 2-thioimidazole-containing low-molecular weight thiol ergothioneine (ET). How the solute binding domain, EgtUC, discriminates among ET and other similar molecules is unknown. Here, we use a "chimeric" mutagenesis strategy and two distantly related EgtUCs from to show that a suite of EgtUC alkyl CH•••S hydrogen bonds to the ET thione S atom are central determinants of molecular recognition. Small perturbations in CH•••S distance and angle give rise to sharply attenuated transport-competent ET-bound "closed" state lifetimes and increased motional disorder in the binding pocket, not around the S atom itself, but distally in weakening NH•••O hydrogen bonds. This work highlights the impact of alkyl CH•••S H bonding in a biological protein-ligand complex in water.

PubMed: 41719410
DOI: 10.1126/sciadv.aeb0426

Experimental method

X-RAY DIFFRACTION (2.14 Å)