Page last updated: 2024-10-24

peptidyl-methionine modification

Definition

Target type: biologicalprocess

The modification of peptidyl-methionine. [GOC:go_curators]

Peptidyl-methionine modification is a crucial post-translational modification that plays a vital role in protein function and regulation. This process typically occurs after the initial translation of a protein, where a methionine residue is often found at the N-terminus. The modification can occur through various pathways, each with distinct enzymatic machinery and outcomes. Here's a detailed description:

* **N-terminal Methionine Removal:** The most common peptidyl-methionine modification involves the removal of the initiating methionine residue from the N-terminus of a protein. This is catalyzed by methionine aminopeptidases (MetAPs), which are ubiquitous enzymes found in all domains of life. MetAPs recognize and cleave the N-terminal methionine if the following residue is not proline, and if the penultimate residue is not acidic (glutamate or aspartate). This removal is essential for the correct folding and function of many proteins.

* **Formylmethionine Removal:** In bacteria and organelles like mitochondria and chloroplasts, the initiating methionine is formylated, resulting in formylmethionine (fMet). fMet removal is catalyzed by deformylase (DEF), which removes the formyl group from fMet. This step is crucial for protein maturation and interaction with downstream chaperones and protein folding machinery.

* **Methionine Oxidation:** Methionine can be oxidized to methionine sulfoxide (MetO), a reversible modification that can affect protein structure and function. The oxidation can be catalyzed by reactive oxygen species (ROS) like hydrogen peroxide. MetO formation can be detrimental, leading to protein misfolding and aggregation. However, it can also serve as a signaling mechanism, regulating protein activity and stability.

* **Methionine Acetylation:** Methionine acetylation involves the attachment of an acetyl group to the amino group of the methionine residue. This modification can occur at internal methionine residues and is catalyzed by N-terminal acetyltransferases (NATs). Methionine acetylation is implicated in various cellular processes, including protein stability, localization, and interaction with other proteins.

* **Other Modifications:** Other less common modifications of methionine residues include methylation, phosphorylation, and ubiquitination. These modifications can affect protein function and regulation in specific contexts.

In summary, peptidyl-methionine modification is a dynamic process that can significantly influence protein structure, function, and stability. Understanding these modifications is crucial for deciphering the intricate mechanisms of protein biology and for developing strategies to target specific modifications for therapeutic purposes.'
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Proteins (3)

ProteinDefinitionTaxonomy
Peptide deformylase, mitochondrialA peptide deformylase, mitochondrial that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q9HBH1]Homo sapiens (human)
Methionine aminopeptidase 1A methionine aminopeptidase 1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P53582]Homo sapiens (human)
Methionine aminopeptidase 2A methionine aminopeptidase 2 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P50579]Homo sapiens (human)

Compounds (20)

CompoundDefinitionClassesRoles
2,2'-dipyridyl2,2'-bipyridine : A bipyridine in which the two pyridine moieties are linked by a bond between positions C-2 and C-2'.

2,2'-Dipyridyl: A reagent used for the determination of iron.
bipyridinechelator;
ferroptosis inhibitor
oxyquinolineOxyquinoline: An antiseptic with mild fungistatic, bacteriostatic, anthelmintic, and amebicidal action. It is also used as a reagent and metal chelator, as a carrier for radio-indium for diagnostic purposes, and its halogenated derivatives are used in addition as topical anti-infective agents and oral antiamebics.

quinolin-8-ol : A monohydroxyquinoline that is quinoline substituted by a hydroxy group at position 8. Its fungicidal properties are used for the control of grey mould on vines and tomatoes.
monohydroxyquinolineantibacterial agent;
antifungal agrochemical;
antiseptic drug;
iron chelator
cloxyquincloxyquin: has antitubercular activity; structure in first sourceorganochlorine compound;
quinolines
ebselenebselen : A benzoselenazole that is 1,2-benzoselenazol-3-one carrying an additional phenyl substituent at position 2. Acts as a mimic of glutathione peroxidase.benzoselenazoleanti-inflammatory drug;
antibacterial agent;
anticoronaviral agent;
antifungal agent;
antineoplastic agent;
antioxidant;
apoptosis inducer;
EC 1.13.11.33 (arachidonate 15-lipoxygenase) inhibitor;
EC 1.13.11.34 (arachidonate 5-lipoxygenase) inhibitor;
EC 1.3.1.8 [acyl-CoA dehydrogenase (NADP(+))] inhibitor;
EC 1.8.1.12 (trypanothione-disulfide reductase) inhibitor;
EC 2.5.1.7 (UDP-N-acetylglucosamine 1-carboxyvinyltransferase) inhibitor;
EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor;
EC 3.1.3.25 (inositol-phosphate phosphatase) inhibitor;
EC 3.4.22.69 (SARS coronavirus main proteinase) inhibitor;
EC 3.5.4.1 (cytosine deaminase) inhibitor;
EC 5.1.3.2 (UDP-glucose 4-epimerase) inhibitor;
enzyme mimic;
ferroptosis inhibitor;
genotoxin;
hepatoprotective agent;
neuroprotective agent;
radical scavenger
thiabendazoleTresaderm: dermatologic soln containing dexamethasone, thiabendazole & neomycin sulfate1,3-thiazoles;
benzimidazole fungicide;
benzimidazoles
antifungal agrochemical;
antinematodal drug
8-hydroxyquinoline-5-sulfonic acid8-hydroxyquinoline-5-sulfonic acid: RN given refers to parent cpd
dimoxylinequinolines
8-hydroxy-2-methylquinoline8-hydroxy-2-methylquinoline: structure in first sourcehydroxyquinoline
nitroxolinenitroxoline : A monohydroxyquinoline in which the hydroxy group is positioned at C-8 with a nitro group trans to it at C-5.

nitroxoline: structure in Merck Index, 9th ed, #6475; RN given refers to parent cpd
C-nitro compound;
monohydroxyquinoline
antifungal agent;
antiinfective agent;
antimicrobial agent;
renal agent
2-(2'-pyridyl)benzimidazole2-(2'-pyridyl)benzimidazole: structure in first source
1-amino-1-phenylmethyl phosphonic acid1-amino-1-phenylmethyl phosphonic acid : A member of the class of phosphonic acids that is phosphonic acid having a amino(phenyl)methyl group attached to the phosphorus.benzenes;
phosphonic acids;
primary amino compound
bis(2-(n-phenylcarboxamido)phenyl)diselenidebis(2-(N-phenylcarboxamido)phenyl)diselenide: selenoorganic cpd which has mitogenic activity in human peripheral leukocytes
bb3497BB3497: peptide deformylase inhibitor; structure in first source
8-(4-benzenesulfonylamino)quinoline8-(4-benzenesulfonylamino)quinoline: has diabetogenic properties; structure given in first source
o-(chloroacetylcarbamoyl)fumagillolO-(chloroacetylcarbamoyl)fumagillol : A carbamate ester that is fumagillol in which the hydroxy group has been converted to the corresponding N-(chloroacetyl)carbamate derivative.

O-(Chloroacetylcarbamoyl)fumagillol: Semisynthetic analog of fumagillin (a cyclohexane-sesquiterpene antibiotic isolated from ASPERGILLUS FUMIGATUS) that inhibits angiogenesis.
carbamate ester;
organochlorine compound;
semisynthetic derivative;
sesquiterpenoid;
spiro-epoxide
angiogenesis inhibitor;
antineoplastic agent;
EC 1.5.1.3 (dihydrofolate reductase) inhibitor;
methionine aminopeptidase 2 inhibitor;
retinoic acid receptor alpha antagonist
actinoninactinonin: natural hydroxamic acid, pseudopeptide antibiotic isolated from Streptomyces species; structure
4,5-dimethylaminobenzylidene-2-thiobarbituric acid
pyridine-2-carboxylic acid thiazol-2-ylamidepyridine-2-carboxylic acid thiazol-2-ylamide: structure in first source
fumagillinantibiotic antifungal drug;
carboxylic ester;
dicarboxylic acid monoester;
meroterpenoid;
organooxygen heterocyclic antibiotic;
spiro-epoxide
angiogenesis inhibitor;
antibacterial drug;
antimicrobial agent;
antiprotozoal drug;
fungal metabolite;
methionine aminopeptidase 2 inhibitor
ppi 2458PPI 2458: a methionine aminopeptidase-2 inhibitor with antirheumatic activity; structure in first source