The origami of thioredoxin‐like folds

Pan, Jonathan L.; Bardwell, James C.A.

doi:10.1110/ps.062268106

Cited by 99 publications

(88 citation statements)

References 78 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Similarly, the single cysteine group (Cys 69 ) of L-FABP in the presence of free radicals can form a sulfonic acid intermediate (Cys-SOH) that is subsequently reduced back by forming a disulfi de bond through the action of thioredoxin ( 49 ). Reactivity of various amino acids was investigated by Xu and Chance ( 48 ).…”

Section: Discussionmentioning

confidence: 99%

Molecular mechanism of recombinant liver fatty acid binding protein's antioxidant activity

Jiang

Gong

She

et al. 2009

Journal of Lipid Research

View full text Add to dashboard Cite

discovered by Ockner et al. in 1972 ( 2 ) and was originally named Z-protein. Since that time, there has been an explosive growth in information regarding the role of L-FABP in cellular homeostasis. While FABPs are present in many tissues, such as heart, brain, intestinal, skin, adipose, muscle, epidermal, ileal, myelin, and testis, L-FABP is found in abundance in hepatocytes where it accounts for ‫ف‬ 2% of the total cellular protein. Although L-FABP is abundant in the liver, it also is present in tissues such as murine alveolar macrophages ( 3 ), kidney ( 4 ), and intestine ( 5 ).L-FABP is made up of 127 amino acids that compose 10 antiparallel ␤ -strands. These stands are organized into two fi ve-stranded ␤ -sheets and two ␣ -helices. The two ␣ -helices are hypothesized to function as a portal that controls entry and release of ligands from the binding pocket created by the ␤ -strands ( 6 ). A large interior water-fi lled cavity forms the confi nes of the ␤ -strands, which serve as the hydrophobic ligand-binding site. L-FABP is able to bind and translocate many lipophilic substrates throughout the cytosol. Some of these substrates include long-chain fatty acids ( 7-9 ), bile acids ( 10 ), eicosanoids ( 11 ), and hypolipidemic drugs ( 12 ). Transfer of these ligands from L-FABP to membranes is thought to occur by a diffusive process; i.e., the ligand fi rst dissociates from the binding pocket and then diffuses to its site of action, while transfer of ligands from other FABPs, such as I-FABP, is thought to occur by a direct collisional interaction ( 13 ). It seems that L-FABP also plays a role in transferring bound ligands into the nucleus. These ligands could activate the peroxisome proliferator-activated receptor ␣ nuclear receptors and

show abstract

Section: Discussionmentioning

confidence: 99%

Molecular mechanism of recombinant liver fatty acid binding protein's antioxidant activity

Jiang

Gong

She

et al. 2009

Journal of Lipid Research

View full text Add to dashboard Cite

show abstract

“…2D); however, Leu-21-Asn-22 are also in extended conformations, and Leu-21 is intimately connected to the hydrophobic protein interior as shown by methyl-methyl NOEs to Leu-61 of the ␣2-␣2Ј helix connector and Met-76 of strand ␤3. The active site disulfide bond, Cys-50 -Cys-53, is located at the beginning of helix ␣2, which is typical for thioredoxin-like oxidoreductases (43). Likewise, the orientation of the longest helix, ␣3, is striking in the sense that it is close to perpendicular to the central ␤-sheet as well as all other ␣-helices.…”

Section: Resultsmentioning

confidence: 95%

Insight into Disulfide Bond Catalysis in Chlamydia from the Structure and Function of DsbH, a Novel Oxidoreductase

Mac

Hacht

Hung

et al. 2008

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

The Chlamydia family of human pathogens uses outer envelope proteins that are highly cross-linked by disulfide bonds but nevertheless keeps an unusually high number of unpaired cysteines in its secreted proteins. To gain insight into chlamydial disulfide bond catalysis, the structure, function, and substrate interaction of a novel periplasmic oxidoreductase, termed DsbH, were determined. The structure of DsbH, its redox potential of ؊269 mV, and its functional properties are similar to thioredoxin and the C-terminal domain of DsbD, i.e. characteristic of a disulfide reductase. As compared with these proteins, the two central residues of the DsbH catalytic motif (CMWC) shield the catalytic disulfide bond and are selectively perturbed by a peptide ligand. This shows that these oxidoreductase family characteristic residues are not only important in determining the redox potential of the catalytic disulfide bond but also in influencing substrate interactions. For DsbH, three functional roles are conceivable; that is, reducing intermolecular disulfides between proteins and small molecules, keeping a specific subset of exported proteins reduced, or maintaining the periplasm of Chlamydia in a generally reducing state.Chlamydia are obligate intracellular eubacteria that are phylogenetically distant from other bacterial divisions (1). Virtually every human being will be infected with Chlamydia pneumoniae in their lifetime, and this organism accounts for ϳ10% of pneumonia cases and 5% of bronchitis cases in the United States (2, 3). Acute infections are usually mild in immunocompetent hosts, but severe pneumonias are observed in immunocompromised patients. Chronic C. pneumoniae infections have been associated with arterial disease (4), where C. pneumoniae act to continuously stimulate inflammation and thereby contribute to stroke and coronary heart disease. Chlamydia have an unique developmental cycle in which the extracellular infectious form, the elementary body, is metabolically inactive and highly resistant to lysis. This is thought to be due in large part to a complex of outer envelope proteins that are highly crosslinked by disulfide bonds (5). Disulfide cross-linked envelope proteins appear to substitute for peptidoglycan in the elementary body (6). This is in contrast to the intracellular, non-infectious but metabolically active reticulate body which employs peptidoglycan (7), like other Gram-negative bacteria. The reliance of the elementary body on disulfide bond-linked proteins suggests that interference with chlamydial disulfide bond catalysis offers a potential avenue for treating chlamydial infections in addition to antibiotics administration. Despite the extensive use of disulfide cross-linked envelope proteins, Chlamydia exhibit an unusually high number of unpaired cysteines in their secreted proteins compared with Escherichia coli. Is the machinery for periplasmic disulfide bond catalysis in Chlamydia different from E. coli?Functional gene assignment of the C. pneumoniae TW183 genome predicts 5 periplasmic...

show abstract

“…PDI-1, PDI-2 in C. elegans), which are involved in disulfide reduction and isomerization, among others. 12,20 As a common feature all members share at least one domain with the so called "trx-fold," which is composed of central b-sheets, surrounded by a-helices. 20 An additional characteristic of thioredoxin superfamily proteins is a CXXC motif in the active site.…”

Section: The Thioredoxin Superfamily -Mediators Between Redox and Promentioning

confidence: 99%

“…12,20 As a common feature all members share at least one domain with the so called "trx-fold," which is composed of central b-sheets, surrounded by a-helices. 20 An additional characteristic of thioredoxin superfamily proteins is a CXXC motif in the active site. This motif differs between the members and can be used for their classification: thioredoxins contain a conserved CGPC motif, while PDIs have CGHC.…”

Section: The Thioredoxin Superfamily -Mediators Between Redox and Promentioning

confidence: 99%

Interplay between redox and protein homeostasis

Feleciano

Arnsburg

Kirstein

2016

Worm

View full text Add to dashboard Cite

The subcellular compartments of eukaryotic cells are characterized by different redox environments. Whereas the cytosol, nucleus and mitochondria are more reducing, the endoplasmic reticulum represents a more oxidizing environment. As the redox level controls the formation of intra-and inter-molecular disulfide bonds, the folding of proteins is tightly linked to its environment. The proteostasis network of each compartment needs to be adapted to the compartmental redox properties. In addition to chaperones, also members of the thioredoxin superfamily can influence the folding of proteins by regulation of cysteine reduction/oxidation. This review will focus on thioredoxin superfamily members and chaperones of C. elegans, which play an important role at the interface between redox and protein homeostasis. Additionally, this review will highlight recent methodological developments on in vivo and in vitro assessment of the redox state and their application to provide insights into the high complexity of redox and proteostasis networks of C. elegans.

show abstract

The origami of thioredoxin‐like folds

Cited by 99 publications

References 78 publications

Molecular mechanism of recombinant liver fatty acid binding protein's antioxidant activity

Molecular mechanism of recombinant liver fatty acid binding protein's antioxidant activity

Insight into Disulfide Bond Catalysis in Chlamydia from the Structure and Function of DsbH, a Novel Oxidoreductase

Interplay between redox and protein homeostasis

Contact Info

Product

Resources

About