Page last updated: 2024-10-24

regulation of endopeptidase activity

Definition

Target type: biologicalprocess

Any process that modulates the frequency, rate or extent of endopeptidase activity, the endohydrolysis of peptide bonds within proteins. [GOC:ai, GOC:hjd]

Endopeptidase activity regulation encompasses a complex and multi-layered process that ensures precise control over protein breakdown within cells and tissues. This intricate mechanism involves a diverse array of regulatory elements, including:

1. **Gene expression:** Transcriptional regulation plays a crucial role in determining the levels of endopeptidase enzymes produced. Transcription factors, signaling pathways, and epigenetic modifications can influence the expression of genes encoding endopeptidases, thereby fine-tuning their production.

2. **Protein synthesis and degradation:** The translation of mRNA into endopeptidase proteins and their subsequent degradation are also subject to regulation. Post-translational modifications, such as phosphorylation, ubiquitination, and glycosylation, can affect the stability, activity, and localization of these enzymes.

3. **Subcellular localization:** Endopeptidases are often localized to specific cellular compartments, such as lysosomes, endosomes, and the extracellular matrix, where they carry out their functions. Targeting mechanisms, involving signal sequences and chaperone proteins, ensure their appropriate localization and prevent unwanted activity in inappropriate cellular compartments.

4. **Activators and inhibitors:** A variety of molecules, including specific substrates, cofactors, and other proteins, can modulate endopeptidase activity. Some molecules act as activators, enhancing the enzyme's catalytic efficiency, while others function as inhibitors, blocking or reducing their activity. These regulatory molecules can be endogenous or exogenous, providing an additional layer of control over endopeptidase function.

5. **Feedback mechanisms:** Endopeptidase activity is often regulated through feedback mechanisms. The products of their enzymatic reactions can influence the activity of the enzyme itself or other enzymes involved in the same pathway, contributing to a dynamic equilibrium of protein breakdown.

6. **Cellular signaling pathways:** Endopeptidases can participate in and be regulated by various cellular signaling pathways, such as the MAPK, PI3K, and TGF-β pathways. These pathways can influence endopeptidase activity through phosphorylation events, transcription factor activation, or other mechanisms, providing a link between external stimuli and endopeptidase regulation.

7. **Cellular stress and disease:** Endopeptidase activity can be altered in response to various cellular stresses, such as oxidative stress, hypoxia, and nutrient deprivation. These changes can contribute to the development of diseases such as cancer, inflammation, and neurodegenerative disorders.

8. **Intercellular communication:** Endopeptidases can be released from cells, acting as extracellular signaling molecules. Their interaction with receptors on other cells can trigger downstream signaling cascades, influencing cellular behavior and tissue homeostasis.

This comprehensive regulatory network ensures the precise control of endopeptidase activity, maintaining protein homeostasis, cell function, and overall organismal health.'
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Proteins (3)

ProteinDefinitionTaxonomy
Proteasome subunit beta type-8A proteasome subunit beta type-8 that is encoded in the genome of human. [PRO:DNx]Homo sapiens (human)
Proteasome subunit alpha type-3A proteasome subunit alpha type-3 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P25788]Homo sapiens (human)
FurinA furin that is encoded in the genome of human. [PRO:CNA, UniProtKB:P09958]Homo sapiens (human)

Compounds (26)

CompoundDefinitionClassesRoles
diminazenediminazene : A triazene derivative that is triazene in which each of the terminal nitrogens is substituted by a 4-carbamimidoylphenyl group.

Diminazene: An effective trypanocidal agent.
carboxamidine;
triazene derivative
antiparasitic agent;
trypanocidal drug
camostatcamostat : A benzoate ester resulting from the formal condensation of the carboxy group of 4-guanidinobenzoic acid with the hydroxy group of 2-(dimethylamino)-2-oxoethyl (4-hydroxyphenyl)acetate. It is a potent inhibitor of the human transmembrane protease serine 2 (TMPRSS2) and its mesylate salt is currently under investigation for its effectiveness in COVID-19 patients.benzoate ester;
carboxylic ester;
diester;
guanidines;
tertiary carboxamide
anti-inflammatory agent;
anticoronaviral agent;
antifibrinolytic drug;
antihypertensive agent;
antineoplastic agent;
antiviral agent;
serine protease inhibitor
chlorpromazinechlorpromazine : A substituted phenothiazine in which the ring nitrogen at position 10 is attached to C-3 of an N,N-dimethylpropanamine moiety.

Chlorpromazine: The prototypical phenothiazine antipsychotic drug. Like the other drugs in this class chlorpromazine's antipsychotic actions are thought to be due to long-term adaptation by the brain to blocking DOPAMINE RECEPTORS. Chlorpromazine has several other actions and therapeutic uses, including as an antiemetic and in the treatment of intractable hiccup.
organochlorine compound;
phenothiazines;
tertiary amine
anticoronaviral agent;
antiemetic;
dopaminergic antagonist;
EC 3.4.21.26 (prolyl oligopeptidase) inhibitor;
phenothiazine antipsychotic drug
bortezomibamino acid amide;
L-phenylalanine derivative;
pyrazines
antineoplastic agent;
antiprotozoal drug;
protease inhibitor;
proteasome inhibitor
sdz 283-910SDZ 283-910: structure in first source
benzyloxycarbonylleucyl-leucyl-leucine aldehydebenzyloxycarbonylleucyl-leucyl-leucine aldehyde: proteasome inhibitor

N-benzyloxycarbonyl-L-leucyl-L-leucyl-L-leucinal : A tripeptide that is L-leucyl-L-leucyl-L-leucine in which the C-terminal carboxy group has been reduced to the corresponding aldehyde and the N-terminal amino group is protected as its benzyloxycarbonyl derivative.
amino aldehyde;
carbamate ester;
tripeptide
proteasome inhibitor
captax1,3-benzothiazole-2-thiol : 1,3-Benzothiazole substituted at the 2-position with a sulfanyl group.

captax: RN given refers to parent cpd
aryl thiol;
benzothiazoles
carcinogenic agent;
metabolite
2-mercaptobenzimidazole2-mercaptobenzimidazole: purine synthesis antimetabolite; RN given refers to parent cpd
2-mercaptobenzoxazolebenzoxazole
5-chloro-1h-benzimidazole-2-thiol5-chloro-1H-benzimidazole-2-thiol: trypanocidal
5-chloro-2-mercaptobenzothiazole
benzyloxycarbonyl-phe-ala-fluormethylketonecathepsin B inhibitor : A cysteine protease inhibitor which inhibits cathepsin B (EC 3.4.22.1).
am 404anilide
lactacystinlactam;
S-substituted L-cysteine
n,n-(4-xylylidene)bisaminoguanidineN,N-(4-xylylidene)bisaminoguanidine: RN in Chemline for di-HCl: 7044-24-8; RN for unspecified HCl: 62580-72-7

N,N'-(p-xylylidene)bis(aminoguanidine) : A guanidine derivative comprised of two carbamimidamido (guanidino) groups, each linked via one of their amino nitrogens to the imino nitrogens of 1,4-phenylenedimethanimine.
clasto-lactacystin beta-lactoneclasto-lactacystin beta-lactone: active metabolite of lactacystin; inhibits 20 S proteasome; structure in first source
marizomibmarizomib: a proteasome inhibitor from a marine bacterium Salinospora; structure in first sourcebeta-lactone;
gamma-lactam;
organic heterobicyclic compound;
organochlorine compound;
salinosporamide
antineoplastic agent;
proteasome inhibitor
carfilzomibepoxide;
morpholines;
tetrapeptide
antineoplastic agent;
proteasome inhibitor
tyropeptin atyropeptin A: proteasome inhibitors produced by Kitasatospora sp. MK993-dF2; structure in first sourcedipeptide
5-(5-nitrothiazol-2-ylthio)-1,3,4-thiadiazol-2-amine5-(5-nitrothiazol-2-ylthio)-1,3,4-thiadiazol-2-amine: structure in first source

halicin : A member of the class of thiadiazoles that is 1,3,4-thiadiazol-2-amine which is substituted by a (5-nitro-1,3-thiazol-2-yl)sulfanediyl group at position 5. It is a c-Jun N-terminal kinase inhibitor (IC50 = 0.7uM) and exhibits antibacterial properties.
1,3-thiazoles;
C-nitro compound;
organic sulfide;
primary amino compound;
thiadiazoles
antibacterial agent;
c-Jun N-terminal kinase inhibitor
pr-957
delanzomibC-terminal boronic acid peptide;
phenylpyridine;
secondary alcohol;
threonine derivative
antineoplastic agent;
apoptosis inducer;
proteasome inhibitor
belactosin abelactosin A: isolated from Streptomyces; structure in first source
oprozomibONX 0912: antineoplastic; an orally active proteasome inhibitor; structure in first source
ixazomibixazomib : A glycine derivative that is the amide obtained by formal condensation of the carboxy group of N-(2,5-dichlorobenzoyl)glycine with the amino group of [(1R)-1-amino-3-methylbutyl]boronic acid. The active metabolite of ixazomib citrate, it is used in combination therapy for treatment of multiple myeloma.

ixazomib: a proteasome inhibitor with antineoplastic activity; MLN2238 is the biologically active form of MLN9708; structure in first source
benzamides;
boronic acids;
dichlorobenzene;
glycine derivative
antineoplastic agent;
apoptosis inducer;
drug metabolite;
orphan drug;
proteasome inhibitor
pi-1840PI-1840: has both antineoplastic and proteasome inhibitory activities; structure in first source