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)
| Protein | Definition | Taxonomy |
|---|---|---|
| Glutaminyl-peptide cyclotransferase | A glutaminyl-peptide cyclotransferase that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q16769] | Homo sapiens (human) |
Compounds (26)
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| catechol | catechols | allelochemical; genotoxin; plant metabolite | |
| histamine | aralkylamino compound; imidazoles | human metabolite; mouse metabolite; neurotransmitter | |
| imidazole | 1H-imidazole : An imidazole tautomer which has the migrating hydrogen at position 1. imidazole: RN given refers to parent cpd | imidazole | |
| 1-methylimidazole | 1-methyl-1H-imidazole : A 1H-imidazole having a methyl substituent at the N-1 position. | imidazoles | |
| oxyquinoline | Oxyquinoline: 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. | monohydroxyquinoline | antibacterial agent; antifungal agrochemical; antiseptic drug; iron chelator |
| benzimidazole | 1H-benzimidazole : The 1H-tautomer of benzimidazole. | benzimidazole; polycyclic heteroarene | |
| histidine | histidine : 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 carboxamide | 5-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-methylimidazole | 4-methylimidazole : Imidazole substituted at position 4 by a methyl group. 4-methylimidazole: RN given refers to parent cpd | imidazoles | carcinogenic agent; reaction intermediate |
| 2-aminobenzimidazole | 2-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 | benzimidazoles | marine xenobiotic metabolite |
| n-acetylimidazole | N-acylimidazole | ||
| 1-(trimethylsilyl)-1h-imidazole | N-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 |
| dazoxiben | dazoxiben: RN given refers to parent cpd | ||
| pyromeconic acid | pyromeconic acid: from herb Dengzhanhua; structure | ||
| 3-methylhistamine | 3-methylhistamine: RN given refers to parent cpd | ||
| n-acetylhistamine | N-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)-pyridinone | 1-hydroxy-2(1H)-pyridinone: structure in first source | ||
| 8-hydroxy-2-quinolinecarboxylic acid | quinolines | ||
| 1-benzylimidazole | 1-benzylimidazole: inhibits human thromboxane synthetase | ||
| 1-(3-aminopropyl)imidazole | imidazoles | ||
| 1-phenylimidazole | 1-phenylimidazole: ligand for cytochrome P-450 & inhibitor of microsomal oxidation | ||
| 1-methyl-3-hydroxypyridine-2-one | |||
| histidinol | L-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-mercaptobenzimidazole | 2-mercaptobenzimidazole: purine synthesis antimetabolite; RN given refers to parent cpd | ||
| thiohydantoins | Thiohydantoins: Sulfur analogs of hydantoins with one or both carbonyl groups replaced by thiocarbonyl groups. | ||
| 4',7-dihydroxyflavone | 4',7-dihydroxyflavone : A dihydroxyflavone in which the two hydroxy substituents are located at positions 4' and 7. 4',7-dihydroxyflavone: inducer of nod gene | dihydroxyflavone | metabolite |