Related Experiment Video
Updated: Jul 7, 2025
12:07
Sequence-specific Labeling of Nucleic Acids and Proteins with Methyltransferases and Cofactor Analogues
Published on: November 22, 2014
14.0K
Methionine gamma lyase: Structure-activity relationships and therapeutic applications
Samanta Raboni1, Serena Faggiano1, Stefano Bettati2
1Department of Food and Drug, University of Parma, Parma, Italy; Institute of Biophysics, National Research Council, Pisa, Italy.
Biochimica Et Biophysica Acta. Proteins and Proteomics
|December 26, 2023
Summary
Methionine gamma lyase (MGL) is an enzyme with therapeutic potential. Structure-function studies reveal its use in cancer and bacterial infection treatments by targeting methionine metabolism.
Area of Science:
- Biochemistry
- Enzymology
- Structural Biology
Background:
- Methionine gamma lyase (MGL) is a pyridoxal 5'-dependent enzyme found in bacteria and plants.
- It catalyzes the conversion of methionine into methanthiol, 2-oxobutanoate, and ammonia.
- MGL belongs to fold type I within its enzyme family.
Purpose of the Study:
- To explore the structure-function relationships of MGL and its variants.
- To investigate the therapeutic applications of MGL in treating diseases like cancer and bacterial infections.
- To review strategies for in vivo delivery of MGL to enhance bioavailability and reduce immunogenicity.
Main Methods:
- Determination of the catalytic mechanism and structure of wild-type MGL and its variants.
- Analysis of MGL in the presence of its natural substrate and sulfur-containing derivatives.
- Review of structure-function relationship studies and therapeutic exploitation strategies.
Main Results:
- Detailed insights into MGL's catalytic mechanism and structural characteristics were obtained.
- Structure-function studies highlighted MGL's potential in cancer therapy by inducing methionine starvation.
- MGL demonstrated utility in antibiotic therapy by converting prodrugs into active agents.
Conclusions:
- MGL exhibits significant therapeutic promise for cancer and bacterial infections.
- Delivery strategies, including PEGylation and vesicle encapsulation with targeting molecules, are crucial for in vivo application.
- Continued research into MGL's structure and function is vital for advancing its clinical use.
Related Concept Videos
01:17Phase II Reactions: Methylation Reactions
193
Methylation is a phase II biotransformation process involving the attachment of a methyl group to a substrate. Enzymes known as methyltransferases orchestrate this reaction.
The mechanism of methylation unfolds in two stages. The first stage sees a methyltransferase enzyme facilitating the transfer of a methyl group from S-adenosylmethionine (SAM) to the substrate, forming S-adenosylhomocysteine (SAH). The second stage involves further metabolism of SAH into homocysteine, which can be recycled...
The mechanism of methylation unfolds in two stages. The first stage sees a methyltransferase enzyme facilitating the transfer of a methyl group from S-adenosylmethionine (SAM) to the substrate, forming S-adenosylhomocysteine (SAH). The second stage involves further metabolism of SAH into homocysteine, which can be recycled...
193
02:34Enzymes
81.5K
Inside living organisms, enzymes act as catalysts for many biochemical reactions involved in cellular metabolism. The role of enzymes is to reduce the activation energies of biochemical reactions by forming complexes with its substrates. The lowering of activation energies favor an increase in the rates of biochemical reactions.
Enzyme deficiencies can often translate into life-threatening diseases. For example, a genetic abnormality resulting in the deficiency of the enzyme G6PD...
Enzyme deficiencies can often translate into life-threatening diseases. For example, a genetic abnormality resulting in the deficiency of the enzyme G6PD...
81.5K
01:22Phase II Reactions: Glutathione Conjugation and Mercapturic Acid Formation
212
Glutathione, a tripeptide made up of glutamate, cysteine, and glycine, is a critical player in the detoxification of drugs and xenobiotics via a process known as glutathione conjugation or mercapturic acid formation. This phase II biotransformation reaction involves the covalent binding of glutathione to a drug or its metabolite, enhancing the compound's water solubility and enabling its excretion.
Several distinctive characteristics distinguish glutathione conjugation from other phase II...
Several distinctive characteristics distinguish glutathione conjugation from other phase II...
212
00:49Ligand Binding and Linkage
4.8K
Allosteric proteins have more than one ligand binding site; the binding of a ligand to any of these sites influences the binding of ligands to the other sites. When a protein is allosteric, its binding sites are called coupled or linked. In the case of enzymes, the site that binds to the substrate is known as the active site and the other site is known as the regulatory site. When a ligand binds to the regulatory site, this leads to conformational changes in the protein that can influence...
4.8K
01:24Phase II Reactions: Acetylation Reactions
229
Acetylation, a phase II biotransformation reaction, introduces an acetyl group to drugs or their metabolites. Acetyltransferase enzymes facilitate this reaction, which resembles α-amino acid conjugation due to the addition of a functional group to the drug molecule.
The substrates for acetylation are typically drugs or their metabolites with an amino, sulfonamide, or hydrazine functional group. Acetylation can occur at several points in the drug molecule, including primary, secondary, and...
The substrates for acetylation are typically drugs or their metabolites with an amino, sulfonamide, or hydrazine functional group. Acetylation can occur at several points in the drug molecule, including primary, secondary, and...
229