Page last updated: 2024-10-24

maintenance of translational fidelity

Definition

Target type: biologicalprocess

Suppression of the occurrence of translational errors, such as codon-anticodon mis-paring, during the process of translation of a protein using an mRNA template. [GOC:hjd, ISBN:9781936113460, PMID:21841312]

Maintenance of translational fidelity is a critical process ensuring accurate protein synthesis. This involves minimizing errors in mRNA decoding and protein assembly, thus producing functional proteins. The fidelity of translation is maintained by a multi-layered system involving:

1. **mRNA Selection and Recognition:** Ribosomes select the correct mRNA transcript for translation through specific interactions between the mRNA and ribosomal RNA (rRNA). This includes recognition of the 5' cap, Shine-Dalgarno sequence, and initiation codon.
2. **tRNA Selection:** tRNA molecules, carrying amino acids, must be accurately matched to their corresponding codons on the mRNA. This involves:
* **Proofreading by the ribosome:** The ribosome can detect and reject mismatched tRNA molecules during the decoding process, providing a primary level of fidelity.
* **Aminoacyl-tRNA synthetases:** These enzymes attach the correct amino acid to each tRNA molecule. They have editing mechanisms to ensure accuracy in amino acid attachment.
3. **Ribosomal Conformation:** The ribosome structure dynamically changes during translation, influencing the efficiency of decoding and protein synthesis. These conformational changes contribute to fidelity by ensuring proper interactions between mRNA, tRNA, and ribosomal proteins.
4. **Quality Control Mechanisms:** Additional mechanisms monitor the quality of protein synthesis and can initiate pathways to degrade misfolded or incomplete proteins. This includes:
* **Non-stop mRNA decay:** This pathway removes mRNAs lacking a stop codon, preventing the production of truncated proteins.
* **Ribosome-associated quality control (RQC):** This system identifies and degrades misfolded proteins by ribosome stalling and ubiquitination.

These mechanisms work together to maintain the accuracy of protein synthesis. Errors in translation can lead to the production of non-functional or even harmful proteins, contributing to various diseases and cellular dysfunction.'
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Proteins (5)

ProteinDefinitionTaxonomy
30S ribosomal protein S5A small ribosomal subunit protein uS5 that is encoded in the genome of Escherichia coli K-12. [PRO:DNx, UniProtKB:P0A7W1]Escherichia coli K-12
30S ribosomal protein S4A small ribosomal subunit protein uS4 that is encoded in the genome of Escherichia coli K-12. [PRO:DNx, UniProtKB:P0A7V8]Escherichia coli K-12
30S ribosomal protein S12A small ribosomal subunit protein uS12 that is encoded in the genome of Escherichia coli K-12. [PRO:DNx, UniProtKB:P0A7S3]Escherichia coli K-12
40S ribosomal protein S12A small ribosomal subunit protein eS12 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P25398]Homo sapiens (human)
40S ribosomal protein S23A eukaryotic-type small ribosomal subunit protein uS12 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P62266]Homo sapiens (human)

Compounds (23)

CompoundDefinitionClassesRoles
chloramphenicolAmphenicol: Chloramphenicol and its derivatives.C-nitro compound;
carboxamide;
diol;
organochlorine compound
antibacterial drug;
antimicrobial agent;
Escherichia coli metabolite;
geroprotector;
Mycoplasma genitalium metabolite;
protein synthesis inhibitor
framycetinframycetin : A tetracyclic antibacterial agent derived from neomycin, being a glycoside ester of neamine and neobiosamine B.

Framycetin: A component of NEOMYCIN that is produced by Streptomyces fradiae. On hydrolysis it yields neamine and neobiosamine B. (From Merck Index, 11th ed)
aminoglycosideallergen;
antibacterial drug;
Escherichia coli metabolite
erythromycinerythromycin : Any of several wide-spectrum macrolide antibiotics obtained from actinomycete Saccharopolyspora erythraea (formerly known as Streptomyces erythraeus).

erythromycin A : An erythromycin that consists of erythronolide A having 2,6-dideoxy-3-C-methyl-3-O-methyl-alpha-L-ribo-hexopyranosyl and 3,4,6-trideoxy-3-(dimethylamino)-beta-D-xylo-hexopyranosyl residues attahced at positions 4 and 6 respectively.

Erythromycin: A bacteriostatic antibiotic macrolide produced by Streptomyces erythreus. Erythromycin A is considered its major active component. In sensitive organisms, it inhibits protein synthesis by binding to 50S ribosomal subunits. This binding process inhibits peptidyl transferase activity and interferes with translocation of amino acids during translation and assembly of proteins.
cyclic ketone;
erythromycin
neamineneamine : 2-Deoxy-D-streptamine glycosylated at the 4-oxygen with a 6-amino-alpha-D-glucosaminyl group.

neamine: fragment of NEOMYCIN B; structure in first source
2,6-dideoxy-alpha-D-glucoside;
aminoglycoside
antibacterial agent
florfenicolflorfenicol : A carboxamide that is the N-dichloroacetyl derivative of (1R,2S)-2-amino-3-fluoro-1-[4-(methanesulfonyl)phenyl]propan-1-ol. A synthetic veterinary antibiotic that is used for treatment of bovine respiratory disease and foot rot; also used in aquaculture.

florfenicol: structure given in first source
organochlorine compound;
organofluorine compound;
secondary alcohol;
secondary carboxamide;
sulfone
antimicrobial agent
antibiotic g 418antibiotic G 418: from Micromonospora rhodorangea
paromomycinparomomycin : An amino cyclitol glycoside that is the 1-O-(2-amino-2-deoxy-alpha-D-glucopyranoside) and the 3-O-(2,6-diamino-2,6-dideoxy-beta-L-idopyranosyl)-beta-D-ribofuranoside of 4,6-diamino-2,3-dihydroxycyclohexane (the 1R,2R,3S,4R,6S diastereoisomer). It is obtained from various Streptomyces species. A broad-spectrum antibiotic, it is used (generally as the sulfate salt) for the treatment of acute and chronic intestinal protozoal infections, but is not effective for extraintestinal protozoal infections. It is also used as a therapeutic against visceral leishmaniasis.

Paromomycin: An aminoglycoside antibacterial and antiprotozoal agent produced by species of STREPTOMYCES.
amino cyclitol glycoside;
aminoglycoside antibiotic
anthelminthic drug;
antibacterial drug;
antiparasitic agent;
antiprotozoal drug
puromycinpuromycinsantiinfective agent;
antimicrobial agent;
antineoplastic agent;
EC 3.4.11.14 (cytosol alanyl aminopeptidase) inhibitor;
EC 3.4.14.2 (dipeptidyl-peptidase II) inhibitor;
nucleoside antibiotic;
protein synthesis inhibitor
netilmicinNetilmicin: Semisynthetic 1-N-ethyl derivative of SISOMYCIN, an aminoglycoside antibiotic with action similar to gentamicin, but less ear and kidney toxicity.
linezolidacetamides;
morpholines;
organofluorine compound;
oxazolidinone
antibacterial drug;
protein synthesis inhibitor
zithromaxazithromycin : A macrolide antibiotic useful for the treatment of bacterial infections.

Azithromycin: A semi-synthetic macrolide antibiotic structurally related to ERYTHROMYCIN. It has been used in the treatment of Mycobacterium avium intracellulare infections, toxoplasmosis, and cryptosporidiosis.
macrolide antibioticantibacterial drug;
environmental contaminant;
xenobiotic
tiamulintiamulin : A carbotricyclic compound that is pleuromutilin in which the hydroxyacetate group is replaced by a 2-{[2-(diethylamino)ethyl]sulfanyl}acetate group. An antibacterial drug, tiamulin is used in veterinary medicine (generally as its hydrogen fumarate salt) for the treatment of swine dysentery caused by Serpulina hyodysenteriae.

tiamulin: 81723 HFU and tiamutin are for fumarate salt; prevents senescence in ascomycete; pleuromutilin derivative; RN given refers to ((3aS-(3aalpha,4beta,5alpha,6alpha,8beta,9alpha,9abeta,10S*))-isomer
carbotricyclic compound;
carboxylic ester;
cyclic ketone;
organic sulfide;
secondary alcohol;
semisynthetic derivative;
tertiary amino compound;
tetracyclic diterpenoid
antibacterial drug
hmr 3647
josamycinacetate ester;
aldehyde;
disaccharide derivative;
glycoside;
macrolide antibiotic;
tertiary alcohol;
tertiary amino compound
antibacterial drug;
metabolite
albocyclinealbocycline: macrolide antibiotic isolated from Streptomyces bruneogriseus nov. sp. MCRL-0129; specifically anti-staphylococcal, including antibiotic-resistant strains; structuremacrolide
evernimicin
gentamicin sulfate
gentamicin sulfate
pristinamycin iibvirginiamycin M2: structure in first source
cem 101solithromycin: an antibacterial fluoroketolide; structure in first source
tetracyclinetetracycline : A broad-spectrum polyketide antibiotic produced by the Streptomyces genus of actinobacteria.

Tetracycline: A naphthacene antibiotic that inhibits AMINO ACYL TRNA binding during protein synthesis.
eravacyclineeravacycline: has antibacterial activitytetracyclines
PF-06446846PF-06446846 : A triazolopyridine that is 3H-[1,2,3]triazolo[4,5-b]pyridine substituted by a 4-{(3-chloropyridin-2-yl)[(3R)-piperidin-3-yl]carbamoyl}phenyl group at position 3. It is a potent inhibitor of PCSK9.

PF-06446846: inhibits translation of PCSK9 ;structure in first source
benzamides;
monochloropyridine;
piperidines;
tertiary carboxamide;
triazolopyridine
antilipemic drug;
EC 3.4.21.61 (kexin) inhibitor