Page last updated: 2024-10-24

protein maturation by [2Fe-2S] cluster transfer

Definition

Target type: biologicalprocess

The transfer of an assembled [2Fe-2S] cluster from a scaffold protein to an acceptor protein that contributes to the attainment of the full functional capacity of a protein. [PMID:23615440]

Protein maturation by [2Fe-2S] cluster transfer is a vital biological process that ensures the proper folding and function of a wide array of proteins involved in diverse cellular functions. The [2Fe-2S] cluster, a prosthetic group composed of two iron atoms and two sulfide ions, serves as a crucial cofactor for numerous enzymes, facilitating electron transfer, redox reactions, and other critical enzymatic activities. This process typically involves a series of intricate steps, orchestrated by specialized proteins and chaperones, ensuring the accurate and efficient delivery of the [2Fe-2S] cluster to its target protein.

The first step involves the biosynthesis of the [2Fe-2S] cluster itself, often within a dedicated protein scaffold termed a scaffold protein. These proteins, often containing a conserved cysteine-rich domain, play a critical role in assembling the iron-sulfur cluster and protecting it from degradation. Once assembled, the [2Fe-2S] cluster must be transferred to the target protein, a process facilitated by specific [2Fe-2S] cluster transferases. These enzymes possess distinct structural features that allow them to bind and deliver the [2Fe-2S] cluster to the target protein in a controlled manner. The transferase typically interacts with both the scaffold protein and the target protein, ensuring the precise delivery of the cluster.

The target protein often undergoes a conformational change upon receiving the [2Fe-2S] cluster, leading to its proper folding and activation. This change in conformation can be triggered by the cluster's presence, which can induce specific interactions within the protein structure, stabilizing a particular fold. In some cases, the [2Fe-2S] cluster may directly participate in the catalytic activity of the target protein. The cluster's redox properties, for example, can facilitate electron transfer reactions within the active site of the enzyme.

The [2Fe-2S] cluster transfer process is often coupled with other protein maturation events, ensuring a coordinated and efficient assembly of functional proteins. For instance, in some cases, the transferase may also participate in the folding or assembly of the target protein, further contributing to its proper function.

The fidelity of [2Fe-2S] cluster transfer is critical for cellular function. Errors in this process can lead to misfolded or inactive proteins, potentially disrupting essential cellular pathways and contributing to disease. Therefore, the precise and regulated transfer of [2Fe-2S] clusters is tightly controlled, ensuring the correct delivery and integration of these cofactors into their target proteins, maintaining cellular homeostasis and ensuring proper protein function.'
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Proteins (1)

ProteinDefinitionTaxonomy
CDGSH iron-sulfur domain-containing protein 1A CDGSH iron-sulfur domain-containing protein 1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q9NZ45]Homo sapiens (human)

Compounds (17)

CompoundDefinitionClassesRoles
4-amino-1,8-naphthalimide4-amino-1,8-naphthalimide: inhibits ADP-ribosylation; sometimes abreviated as 4-AN;benzoisoquinoline;
dicarboximide
tyrphostin ag 1024tyrphostin AG 1024: modulates radiosensitivity in human breast cancer cells; also an IGF1 receptor inhibitoralkylbenzene
carbonyl cyanide m-chlorophenyl hydrazoneCarbonyl Cyanide m-Chlorophenyl Hydrazone: A proton ionophore. It is commonly used as an uncoupling agent and inhibitor of photosynthesis because of its effects on mitochondrial and chloroplast membranes.

CCCP : A member of the class of monochlorobenzenes that is benzene substituted by 2-(1,3-dinitrilopropan-2-ylidene)hydrazinyl and chloro groups at positions 1 and 3, respectively. It is a mitochondrial depolarizing agent that induces reactive oxygen species mediated cell death.
hydrazone;
monochlorobenzenes;
nitrile
antibacterial agent;
geroprotector;
ionophore
furosemidefurosemide : A chlorobenzoic acid that is 4-chlorobenzoic acid substituted by a (furan-2-ylmethyl)amino and a sulfamoyl group at position 2 and 5 respectively. It is a diuretic used in the treatment of congestive heart failure.

Furosemide: A benzoic-sulfonamide-furan. It is a diuretic with fast onset and short duration that is used for EDEMA and chronic RENAL INSUFFICIENCY.
chlorobenzoic acid;
furans;
sulfonamide
environmental contaminant;
loop diuretic;
xenobiotic
gemfibrozilaromatic etherantilipemic drug
glyburideglyburide : An N-sulfonylurea that is acetohexamide in which the acetyl group is replaced by a 2-(5-chloro-2-methoxybenzamido)ethyl group.

Glyburide: An antidiabetic sulfonylurea derivative with actions like those of chlorpropamide
monochlorobenzenes;
N-sulfonylurea
anti-arrhythmia drug;
EC 2.7.1.33 (pantothenate kinase) inhibitor;
EC 3.6.3.49 (channel-conductance-controlling ATPase) inhibitor;
hypoglycemic agent
pioglitazonepioglitazone : A member of the class of thiazolidenediones that is 1,3-thiazolidine-2,4-dione substituted by a benzyl group at position 5 which in turn is substituted by a 2-(5-ethylpyridin-2-yl)ethoxy group at position 4 of the phenyl ring. It exhibits hypoglycemic activity.

Pioglitazone: A thiazolidinedione and PPAR GAMMA agonist that is used in the treatment of TYPE 2 DIABETES MELLITUS.
aromatic ether;
pyridines;
thiazolidinediones
antidepressant;
cardioprotective agent;
EC 2.7.1.33 (pantothenate kinase) inhibitor;
EC 6.2.1.3 (long-chain-fatty-acid--CoA ligase) inhibitor;
ferroptosis inhibitor;
geroprotector;
hypoglycemic agent;
insulin-sensitizing drug;
PPARgamma agonist;
xenobiotic
ursodeoxycholic acidursodeoxycholate : A bile acid anion that is the conjugate base of ursodeoxycholic acid, obtained by deprotonation of the carboxy group; major species at pH 7.3.

ursodeoxycholic acid : A bile acid found in the bile of bears (Ursidae) as a conjugate with taurine. Used therapeutically, it prevents the synthesis and absorption of cholesterol and can lead to the dissolution of gallstones.

Ursodeoxycholic Acid: An epimer of chenodeoxycholic acid. It is a mammalian bile acid found first in the bear and is apparently either a precursor or a product of chenodeoxycholate. Its administration changes the composition of bile and may dissolve gallstones. It is used as a cholagogue and choleretic.
bile acid;
C24-steroid;
dihydroxy-5beta-cholanic acid
human metabolite;
mouse metabolite
rosiglitazoneaminopyridine;
thiazolidinediones
EC 6.2.1.3 (long-chain-fatty-acid--CoA ligase) inhibitor;
ferroptosis inhibitor;
insulin-sensitizing drug
tyrphostin 8tyrphostin 8: a tyrosine kinase inhibitor (a tyrphostin)phenols
curcumincurcumin : A beta-diketone that is methane in which two of the hydrogens are substituted by feruloyl groups. A natural dyestuff found in the root of Curcuma longa.

Curcumin: A yellow-orange dye obtained from tumeric, the powdered root of CURCUMA longa. It is used in the preparation of curcuma paper and the detection of boron. Curcumin appears to possess a spectrum of pharmacological properties, due primarily to its inhibitory effects on metabolic enzymes.
aromatic ether;
beta-diketone;
diarylheptanoid;
enone;
polyphenol
anti-inflammatory agent;
antifungal agent;
antineoplastic agent;
biological pigment;
contraceptive drug;
dye;
EC 1.1.1.205 (IMP dehydrogenase) inhibitor;
EC 1.1.1.21 (aldehyde reductase) inhibitor;
EC 1.1.1.25 (shikimate dehydrogenase) inhibitor;
EC 1.6.5.2 [NAD(P)H dehydrogenase (quinone)] inhibitor;
EC 1.8.1.9 (thioredoxin reductase) inhibitor;
EC 2.7.10.2 (non-specific protein-tyrosine kinase) inhibitor;
EC 3.5.1.98 (histone deacetylase) inhibitor;
flavouring agent;
food colouring;
geroprotector;
hepatoprotective agent;
immunomodulator;
iron chelator;
ligand;
lipoxygenase inhibitor;
metabolite;
neuroprotective agent;
nutraceutical;
radical scavenger
kaempferol7-hydroxyflavonol;
flavonols;
tetrahydroxyflavone
antibacterial agent;
geroprotector;
human blood serum metabolite;
human urinary metabolite;
human xenobiotic metabolite;
plant metabolite
as 605240(5Z)-5-(quinoxalin-6-ylmethylidene)-1,3-thiazolidine-2,4-dione : A quinoxaline derivative that is quinoxaline in which the hydrogen at position 6 is replaced by a (2,4-dioxo-1,3-thiazolidin-5-ylidene)methyl group. It is a potent inhibitor of the PI3Kgamma, with an IC50 of 8 nM and inhibits the progression of joint inflammation and damage in both lymphocyte-independent and dependent mouse models of rheumatoid arthritis.

5-quinoxalin-6-ylmethylenethiazolidine-2,4-dione: a PI3Kgamma inhibitor; structure in first source
quinoxaline derivative;
thiazolidinediones
anti-inflammatory agent;
antirheumatic drug;
EC 2.7.1.137 (phosphatidylinositol 3-kinase) inhibitor
nitrofurantoinnitrofurantoin : An imidazolidine-2,4-dione that is hydantoin substituted at position 1 by a [(5-nitro-2-furyl)methylene]amino group. An antibiotic that damages bacterial DNA.

Nitrofurantoin: A urinary anti-infective agent effective against most gram-positive and gram-negative organisms. Although sulfonamides and antibiotics are usually the agents of choice for urinary tract infections, nitrofurantoin is widely used for prophylaxis and long-term suppression.
imidazolidine-2,4-dione;
nitrofuran antibiotic;
organonitrogen heterocyclic antibiotic;
organooxygen heterocyclic antibiotic
antibacterial drug;
antiinfective agent;
hepatotoxic agent
dantrolene
3-aminopyridine-2-carboxaldehyde thiosemicarbazone3-aminopyridine-2-carboxaldehyde thiosemicarbazone: a neuroprotective agent; structure given in first source
tryprostatin atryprostatin A : A cyclic dipeptide that is brevianamide F (cyclo-L-Trp-L-Pro) substituted at positions 2 and 6 on the indole ring by prenyl and methoxy groups respectively.

tryprostatin A: isolated from Aspergillus fumigatus; a mammalian cell cycle inhibitor; structure given in first source
aromatic ether;
dipeptide;
indole alkaloid;
indoles;
pyrrolopyrazine
breast cancer resistance protein inhibitor