Related Experiment Video
Updated: Jun 24, 2026
05:58
Site-Specific Lysine Lactylation via Genetic Code Expansion in E. coli and Mammalian Cells
Published on: February 24, 2026
Lacticin 481 synthetase as a general serine/threonine kinase
Young Ok You1, Matthew R Levengood, L A Furgerson Ihnken
1Department of Biochemistry and Howard Hughes Medical Institute, University of Illinois at Urbana-Champaign, 600 South Mathews Avenue, Urbana, IL 61801, USA.
ACS Chemical Biology
|March 19, 2009
Summary
Researchers utilized a lantibiotic synthetase to create modified peptides, including phosphopeptides and glycopeptides. This method allows for general, mild, and non-sequence-specific introduction of posttranslational modifications for functional studies.
Area of Science:
- Biochemistry
- Synthetic Biology
- Peptide Chemistry
Background:
- Posttranslational modifications (PTMs) are crucial for protein function.
- Introducing PTMs generally and non-sequence-specifically is challenging.
- Lantibiotic synthetases offer a unique platform for peptide modification.
Purpose of the Study:
- To exploit the substrate promiscuity of a lantibiotic synthetase for preparing diverse modified peptides.
- To investigate the utility of this method for introducing phosphoserine, O-linked glycopeptide mimics, and lysine analogs.
- To establish a versatile platform for studying PTM functions.
Main Methods:
- Utilized engineered mutants (R399M and T405A) of lacticin 481 synthetase (LctM) for peptide phosphorylation.
- Exploited wild-type LctM to dehydrate peptides, forming dehydroalanine residues.
- Performed nucleophilic additions to dehydroalanine for generating modified lysine analogs and glycopeptide mimics.
Main Results:
- Demonstrated broad substrate scope for serine phosphorylation, even at distant sites.
- Successfully generated phosphopeptides, glycopeptide mimics (using thiosaccharides), and N-acetylated/methylated lysine mimics.
- Showcased the ability to modify peptides in a general, mild, and non-sequence-specific manner.
Conclusions:
- Lantibiotic synthetase LctM is a versatile tool for creating diverse posttranslationally modified peptides.
- This method provides a powerful approach for synthesizing PTM analogs for functional studies.
- The non-sequence-specific nature facilitates broad applicability in chemical biology and drug discovery.
More Related Videos
Related Concept Videos
01:20The JAK-STAT Signaling Pathway
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
01:18ATP Synthase: Structure
ATP synthase or ATPase is among the most conserved proteins found in bacteria, mammals, and plants. This enzyme can catalyze a forward reaction in response to the electrochemical gradient, producing ATP from ADP and inorganic phosphate. ATP synthase can also work in a reverse direction by hydrolyzing ATP and generating an electrochemical gradient. Different forms of ATP synthases have evolved special features to meet the specific demands of the cell. Based on their specific feature, ATP...
01:57Protein Complexes with Interchangeable Parts
Groups of proteins may form a complex where each protein in this complex has a different role in the overall execution of the complex’s function. Often some of the proteins in the complex can be replaced by a closely related variant to give a complex that contains many of the same components yet is functionally distinct.
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order to...
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order to...
01:22PI3K/mTOR/AKT Signaling Pathway
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a rapamycin-insensitive companion...
01:22Amplifying Signals via Enzymatic Cascade
When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze the...
01:09Cytoskeletal Linker Proteins - Plakins
Plakins are large proteins with binding domains for microtubules, microfilaments, intermediate filaments, and membrane-associated protein complexes at cell junctions. Plakin functions are evolutionarily conserved and are primarily involved in organizing the different components of the cytoskeleton by crosslinking them to each other and connecting them to the cell-matrix and cell adhesion complexes. They are also known to interact with signal transducers, serve as scaffolds for signaling...