TldD/TldE peptidases and N-deacetylases: A structurally unique yet ubiquitous protein family in the microbial metabolism

0562368 - MBÚ 2023 RIV DE eng J - Journal Article
Vobruba, Šimon - Kadlčík, Stanislav - Janata, Jiří - Kameník, Zdeněk
TldD/TldE peptidases and N-deacetylases: A structurally unique yet ubiquitous protein family in the microbial metabolism.
Microbiological Research. Roč. 265, Dec (2022), č. článku 127186. ISSN 0944-5013. E-ISSN 1618-0623
R&D Projects: GA ČR(CZ) GJ20-09811Y; GA MŠMT(CZ) LX22NPO5103
Grant - others:AV ČR(CZ) LQ200202002
Program: Prémie Lumina quaeruntur
Institutional support: RVO:61388971
Keywords : Deacetylases * Lincosamides * Microbial specialized metabolism * Peptidases * Protein structure * Ribosomally synthesized post-translationally modified peptides * TldD/TldE
OECD category: Microbiology
Impact factor: 6.7, year: 2022
Method of publishing: Open access
https://www.sciencedirect.com/science/article/pii/S0944501322002269?via%3Dihub

Here we provide a review on TldD/TldE family proteins, summarizing current knowledge and outlining further research perspectives. Despite being widely distributed in bacteria and archaea, TldD/TldE proteins have been escaping attention for a long time until several recent reports pointed to their unique features. Specifically, TldD/TldE generally act as peptidases, though some of them turned out to be N-deacetylases. Biological function of TldD/TldE has been extensively described in bacterial specialized metabolism, in which they participate in the biosynthesis of lincosamide antibiotics (as N-deacetylases), and in the biosynthesis of ribosomally synthesized and post-translationally modified bioactive peptides (as peptidases). These enzymes possess special position in the relevant biosynthesis since they convert non-bioactive intermediates into bioactive metabolites. Further, based on a recent study of Escherichia coli TldD/TldE, these heterodimeric metallopeptidases possess a new protein fold exhibiting several structural features with no precedent in the Protein Data Bank. The most interesting ones are structural elements forming metal-containing active site on the inner surface of the catalytically active subunit TldD, in which substrates bind through β sheet interactions in the sequence-independent manner. It results in relaxed substrate specificity of TldD/TldE, which is counterbalanced by enclosing the active centre within the hollow core of the heterodimer and only appropriate substrates can entry through a narrow channel. Based on the published data, we hypothesize a yet unrecognized central metabolic function of TldD/TldE in the degradation of (partially) unfolded proteins, i.e., in protein quality control.
Permanent Link: https://hdl.handle.net/11104/0334708