8IXP

Apo structure of glycosyltransferase LmbT wild type

Summary for 8IXP

• Entry DOI: 10.2210/pdb8ixp/pdb
• Descriptor: Glycosyltransferase (2 entities in total)
• Functional Keywords: lincomycin, glycosyltransferase, biosynthesis, transferase
• Biological source: Streptomyces lincolnensis
• Total number of polymer chains: 4
• Total formula weight: 195636.66

Authors

Mori, T.,Sun, X.,Abe, I. (deposition date: 2023-04-02, release date: 2024-04-03, Last modification date: 2024-10-30)

Primary citation

Mori, T.,Sun, X.,Kadlcik, S.,Janata, J.,Abe, I.
Structure-Function Analysis of the S-Glycosylation Reaction in the Biosynthesis of Lincosamide Antibiotics.
Angew.Chem.Int.Ed.Engl., 62:e202304989-e202304989, 2023

PubMed Abstract: The S-glycosyltransferase LmbT, involved in the biosynthesis of lincomycin A, is the only known enzyme that catalyzes the enzymatic incorporation of rare amino acid L-ergothioneine (EGT) into secondary metabolites. Here, we show the structure and function analyses of LmbT. Our in vitro analysis of LmbT revealed that the enzyme shows promiscuous substrate specificity toward nitrogenous base moieties in the generation of unnatural nucleotide diphosphate (NDP)-D-α-D-lincosamides. Furthermore, the X-ray crystal structures of LmbT in its apo form and in complex with substrates indicated that the large conformational changes of the active site occur upon binding of the substrates, and that EGT is strictly recognized by salt-bridge and cation-π interactions with Arg260 and Trp101, respectively. The structure of LmbT in complex with its substrates, the docking model with the EGT-S-conjugated lincosamide, and the structure-based site-directed mutagenesis analysis revealed the structural details of the LmbT-catalyzed S 2-like S-glycosylation reaction with EGT.

PubMed: 37222528
DOI: 10.1002/anie.202304989

Experimental method

X-RAY DIFFRACTION (2.45 Å)