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Structure-Function Analysis of the S-Glycosylation Reaction in the Biosynthesis of Lincosamide Antibiotics
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SYSNO ASEP 0573702 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Structure-Function Analysis of the S-Glycosylation Reaction in the Biosynthesis of Lincosamide Antibiotics Author(s) Mori, T. (JP)
Sun, X. (JP)
Kadlčík, Stanislav (MBU-M) RID, ORCID
Janata, Jiří (MBU-M) RID, ORCID
Abe, I. (JP)Article number e2023049 Source Title Angewandte Chemie - International Edition. - : Wiley - ISSN 1433-7851
Roč. 62, č. 29 (2023)Number of pages 5 s. Language eng - English Country DE - Germany Keywords LmbT ; S-glycosyltransferase ; lincomycin ; ergothioneine ; protein structure Subject RIV EE - Microbiology, Virology OECD category Microbiology R&D Projects GJ20-09811Y GA ČR - Czech Science Foundation (CSF) LX22NPO5103 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Method of publishing Open access Institutional support MBU-M - RVO:61388971 UT WOS 001008371000001 EID SCOPUS 85161681664 DOI https://doi.org/10.1002/anie.202304989 Annotation 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 SN2-like S-glycosylation reaction with EGT. Workplace Institute of Microbiology Contact Eliška Spurná, eliska.spurna@biomed.cas.cz, Tel.: 241 062 231 Year of Publishing 2024 Electronic address https://onlinelibrary.wiley.com/doi/10.1002/anie.202304989
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