dehydrobutyrine has been researched along with lanthionine* in 3 studies
3 other study(ies) available for dehydrobutyrine and lanthionine
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LanCLs add glutathione to dehydroamino acids generated at phosphorylated sites in the proteome.
Enzyme-mediated damage repair or mitigation, while common for nucleic acids, is rare for proteins. Examples of protein damage are elimination of phosphorylated Ser/Thr to dehydroalanine/dehydrobutyrine (Dha/Dhb) in pathogenesis and aging. Bacterial LanC enzymes use Dha/Dhb to form carbon-sulfur linkages in antimicrobial peptides, but the functions of eukaryotic LanC-like (LanCL) counterparts are unknown. We show that LanCLs catalyze the addition of glutathione to Dha/Dhb in proteins, driving irreversible C-glutathionylation. Chemo-enzymatic methods were developed to site-selectively incorporate Dha/Dhb at phospho-regulated sites in kinases. In human MAPK-MEK1, such "elimination damage" generated aberrantly activated kinases, which were deactivated by LanCL-mediated C-glutathionylation. Surveys of endogenous proteins bearing damage from elimination (the eliminylome) also suggest it is a source of electrophilic reactivity. LanCLs thus remove these reactive electrophiles and their potentially dysregulatory effects from the proteome. As knockout of LanCL in mice can result in premature death, repair of this kind of protein damage appears important physiologically. Topics: Alanine; Aminobutyrates; Animals; Antimicrobial Cationic Peptides; Female; Glutathione; HEK293 Cells; Humans; Male; MAP Kinase Kinase 1; Membrane Proteins; Mice; Mice, Knockout; Mitogen-Activated Protein Kinase Kinases; Phosphate-Binding Proteins; Phosphorylation; Protein Domains; Proteome; Receptors, G-Protein-Coupled; Sulfides | 2021 |
Chapter 21. In vitro studies of lantibiotic biosynthesis.
The lantibiotics are ribosomally synthesized and posttranslationally modified peptide antibiotics containing the thioether crosslinks lanthionine (Lan) and 3-methyllanthionine (MeLan) and typically also the dehydroamino acids dehydroalanine (Dha) and (Z)-dehydrobutyrine (Dhb). These modifications are formed by dehydration of Ser/Thr residues to produce the Dha and Dhb structures, and subsequent conjugate additions of Cys residues onto the unsaturated amino acids to form thioether rings (Lan and MeLan). Several of the enzymatic reactions involved in lantibiotic biosynthesis have been reconstituted in vitro in recent years and these systems as well as a general overview of lantibiotic biosynthesis are discussed in this chapter. Topics: Alanine; Aminobutyrates; Bacteriocins; Molecular Structure; Sulfides | 2009 |
The importance of the leader sequence for directing lanthionine formation in lacticin 481.
Lantibiotics are post-translationally modified peptide antimicrobial agents that are synthesized with an N-terminal leader sequence and a C-terminal propeptide. Their maturation involves enzymatic dehydration of Ser and Thr residues in the precursor peptide to generate unsaturated amino acids, which react intramolecularly with nearby cysteines to form cyclic thioethers termed lanthionines and methyllanthionines. The role of the leader peptide in lantibiotic biosynthesis has been subject to much speculation. In this study, mutations of conserved residues in the leader sequence of the precursor peptide for lacticin 481 (LctA) did not inhibit dehydration and cyclization by lacticin 481 synthetase (LctM) showing that not one specific residue is essential for these transformations. These amino acids may therefore be conserved in the leader sequence of class II lantibiotics to direct other biosynthetic events, such as proteolysis of the leader peptide or transport of the active compound outside the cell. However, introduction of Pro residues into the leader peptide strongly affected the efficiency of dehydration, consistent with recognition of the secondary structure of the leader peptide by the synthetase. Furthermore, the presence of a hydrophobic residue at the position of Leu-7 appears important for enzymatic processing. Based on the data in this work and previous studies, a model for the interaction of LctM with LctA is proposed. The current study also showcases the ability to prepare other lantibiotics in the class II lacticin 481 family, including nukacin ISK-1, mutacin II, and ruminococcin A using the lacticin 481 synthetase. Surprisingly, a conserved Glu located in a ring that appears conserved in many class II lantibiotics, including those not belonging to the lacticin 481 subgroup, is not essential for antimicrobial activity of lacticin 481. Topics: 5' Untranslated Regions; Alanine; Amino Acid Sequence; Aminobutyrates; Bacteriocins; Conserved Sequence; DNA Primers; Enzymes; Gene Expression; Molecular Sequence Data; Mutagenesis, Site-Directed; Plasmids; Sequence Alignment; Sulfides | 2008 |