7TXL

Crystal structure of EgtU solute binding domain from Streptococcus pneumoniae D39 in complex with L-ergothioneine

Summary for 7TXL

• Entry DOI: 10.2210/pdb7txl/pdb
• Descriptor: Choline transporter (Glycine betaine transport system permease protein), trimethyl-[(2S)-1-oxidanyl-1-oxidanylidene-3-(2-sulfanylidene-1,3-dihydroimidazol-4-yl)propan-2-yl]azanium, 1,2-ETHANEDIOL, ... (4 entities in total)
• Functional Keywords: egt, soluble binding protein, sbp, abc transporter, transport protein
• Biological source: Streptococcus pneumoniae serotype 2 (strain D39 / NCTC 7466)
• Total number of polymer chains: 2
• Total formula weight: 62659.39

Authors

Zhang, Y.,Gonzalez-Gutierrez, G.,Giedroc, D.P. (deposition date: 2022-02-09, release date: 2022-12-21, Last modification date: 2023-10-25)

Primary citation

Zhang, Y.,Gonzalez-Gutierrez, G.,Legg, K.A.,Walsh, B.J.C.,Pis Diez, C.M.,Edmonds, K.A.,Giedroc, D.P.
Discovery and structure of a widespread bacterial ABC transporter specific for ergothioneine.
Nat Commun, 13:7586-7586, 2022

PubMed Abstract: L-Ergothioneine (ET), the 2-thioimidazole derivative of trimethylhistidine, is biosynthesized by select fungi and bacteria, notably Mycobacterium tuberculosis, and functions as a scavenger of reactive oxygen species. The extent to which ET broadly functions in bacterial cells unable to synthesize it is unknown. Here we show that spd_1642-1643 in Streptococcus pneumoniae, a Gram-positive respiratory pathogen, encodes an ET uptake ATP-binding cassette (ABC) transporter, designated EgtU. The solute binding domain (SBD) of EgtU, EgtUC, binds ET with high affinity and exquisite specificity in a cleft between the two subdomains, with cation-π interactions engaging the betaine moiety and a network of water molecules that surround the thioimidazole ring. EgtU is highly conserved among known quaternary amine compound-specific transporters and widely distributed in Firmicutes, including the human pathogens Listeria monocytogenes, as BilEB, Enterococcus faecalis and Staphylococcus aureus. ET increases the chemical diversity of the low molecular weight thiol pool in Gram-positive human pathogens and may contribute to antioxidant defenses in the infected host.

PubMed: 36481738
DOI: 10.1038/s41467-022-35277-3

Experimental method

X-RAY DIFFRACTION (2.44 Å)