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peptidyl-pyroglutamic acid biosynthetic process, using glutaminyl-peptide cyclotransferase

Definition

Target type: biologicalprocess

The chemical reactions and pathways resulting in the formation of peptidyl-pyroglutamic acid, catalyzed by glutaminyl-peptide cyclotransferase. [RESID:AA0031]

Peptidyl-pyroglutamic acid biosynthesis, also known as cyclization of N-terminal glutamine, is a crucial post-translational modification that plays a significant role in various cellular processes. It involves the conversion of an N-terminal glutamine residue into pyroglutamic acid (pGlu), a cyclic form of glutamate. This transformation is catalyzed by the enzyme glutaminyl-peptide cyclotransferase (QPCT), also known as glutaminyl cyclase or pyrrolidone carboxylate synthetase.

The reaction catalyzed by QPCT is a two-step process:

1. **Glutaminyl-peptide cyclotransferase (QPCT) recognizes and binds to the N-terminal glutamine residue of a peptide.** The enzyme's active site specifically interacts with the glutamine side chain.
2. **The enzyme then facilitates the cyclization reaction.** This involves the removal of a water molecule from the glutamine side chain, resulting in the formation of a cyclic structure known as pyroglutamic acid (pGlu).

The formation of pGlu has several important biological consequences:

- **Increased resistance to enzymatic degradation:** pGlu residues are resistant to the action of aminopeptidases, enzymes that cleave N-terminal amino acids. This resistance protects the peptide from degradation, increasing its stability and half-life.
- **Altered peptide conformation:** The presence of pGlu can influence the peptide's structure and conformation. This can affect its biological activity and interactions with other proteins or molecules.
- **Regulation of peptide function:** pGlu formation can serve as a regulatory mechanism, controlling the activity or stability of peptides.

QPCT is a highly conserved enzyme found in various organisms, including bacteria, yeast, and mammals. It is involved in a wide range of biological processes, including:

- **Neuropeptide processing:** pGlu formation is crucial for the processing and activation of several neuropeptides, such as thyrotropin-releasing hormone (TRH), gonadotropin-releasing hormone (GnRH), and substance P.
- **Immune system regulation:** QPCT plays a role in regulating the activity of cytokines, proteins that mediate immune responses.
- **Cellular signaling:** pGlu modification can affect the signaling pathways of various proteins and peptides.
- **Protein folding and stability:** pGlu formation can influence the proper folding and stability of certain proteins.

In summary, the peptidyl-pyroglutamic acid biosynthetic process, catalyzed by glutaminyl-peptide cyclotransferase (QPCT), is an essential post-translational modification that plays a critical role in various biological processes. The formation of pGlu can affect peptide stability, conformation, function, and regulatory mechanisms.'
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Proteins (1)

ProteinDefinitionTaxonomy
Glutaminyl-peptide cyclotransferaseA glutaminyl-peptide cyclotransferase that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q16769]Homo sapiens (human)

Compounds (26)

CompoundDefinitionClassesRoles
catecholcatecholsallelochemical;
genotoxin;
plant metabolite
histaminearalkylamino compound;
imidazoles
human metabolite;
mouse metabolite;
neurotransmitter
imidazole1H-imidazole : An imidazole tautomer which has the migrating hydrogen at position 1.

imidazole: RN given refers to parent cpd
imidazole
1-methylimidazole1-methyl-1H-imidazole : A 1H-imidazole having a methyl substituent at the N-1 position.imidazoles
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
benzimidazole1H-benzimidazole : The 1H-tautomer of benzimidazole.benzimidazole;
polycyclic heteroarene
histidinehistidine : An alpha-amino acid that is propanoic acid bearing an amino substituent at position 2 and a 1H-imidazol-4-yl group at position 3.

Histidine: An essential amino acid that is required for the production of HISTAMINE.

L-histidine : The L-enantiomer of the amino acid histidine.
amino acid zwitterion;
histidine;
L-alpha-amino acid;
polar amino acid zwitterion;
proteinogenic amino acid
algal metabolite;
Escherichia coli metabolite;
human metabolite;
micronutrient;
mouse metabolite;
nutraceutical;
Saccharomyces cerevisiae metabolite
aminoimidazole carboxamide5-aminoimidazole-4-carboxamide : An aminoimidazole in which the amino group is at C-5 with a carboxamido group at C-4.

Aminoimidazole Carboxamide: An imidazole derivative which is a metabolite of the antineoplastic agents BIC and DIC. By itself, or as the ribonucleotide, it is used as a condensation agent in the preparation of nucleosides and nucleotides. Compounded with orotic acid, it is used to treat liver diseases.
aminoimidazole;
monocarboxylic acid amide
mouse metabolite
4-methylimidazole4-methylimidazole : Imidazole substituted at position 4 by a methyl group.

4-methylimidazole: RN given refers to parent cpd
imidazolescarcinogenic agent;
reaction intermediate
2-aminobenzimidazole2-aminobenzimidazole : A member of the class of benzimidazoles that is benzimidazole in which the hydrogen at position 2 is replaced by an amino group.

2-aminobenzimidazole: metabolite of benomyl; RN given refers to parent cpd
benzimidazolesmarine xenobiotic metabolite
n-acetylimidazoleN-acylimidazole
1-(trimethylsilyl)-1h-imidazoleN-trimethylsilylimidazole : A member of the class of imidazoles in which the hydrogen at position 1 is replaced by a trimethylsilyl group. N-trimethylsilylimidazole is a derivatisation agent used in gas chromatography/mass spectrometry applications.imidazoles;
N-silyl compound
chromatographic reagent
dazoxibendazoxiben: RN given refers to parent cpd
pyromeconic acidpyromeconic acid: from herb Dengzhanhua; structure
3-methylhistamine3-methylhistamine: RN given refers to parent cpd
n-acetylhistamineN-acetylhistamine : A member of the class of acetamides that is acetamide comprising histamine having an acetyl group attached to the side-chain amino function.acetamides;
imidazoles
human metabolite
1-hydroxy-2(1h)-pyridinone1-hydroxy-2(1H)-pyridinone: structure in first source
8-hydroxy-2-quinolinecarboxylic acidquinolines
1-benzylimidazole1-benzylimidazole: inhibits human thromboxane synthetase
1-(3-aminopropyl)imidazoleimidazoles
1-phenylimidazole1-phenylimidazole: ligand for cytochrome P-450 & inhibitor of microsomal oxidation
1-methyl-3-hydroxypyridine-2-one
histidinolL-histidinol : An amino alcohol that is propanol substituted by 1H-imidazol-4-yl group at position 3 and an amino group at position 2 (the 2S stereoisomer).amino alcohol;
imidazoles
EC 2.3.1.97 (glycylpeptide N-tetradecanoyltransferase) inhibitor;
Escherichia coli metabolite;
human metabolite;
Saccharomyces cerevisiae metabolite
2-mercaptobenzimidazole2-mercaptobenzimidazole: purine synthesis antimetabolite; RN given refers to parent cpd
thiohydantoinsThiohydantoins: Sulfur analogs of hydantoins with one or both carbonyl groups replaced by thiocarbonyl groups.
4',7-dihydroxyflavone4',7-dihydroxyflavone : A dihydroxyflavone in which the two hydroxy substituents are located at positions 4' and 7.

4',7-dihydroxyflavone: inducer of nod gene
dihydroxyflavonemetabolite