Self-assembly of a robust, reduction-sensitive camptothecin nanotube

2020 ◽  
Vol 56 (71) ◽  
pp. 10337-10340
Author(s):  
Yuan Sun ◽  
Cathleen M. Fry ◽  
Aileen Shieh ◽  
Jon R. Parquette
Keyword(s):  
Drug Release ◽  
Disulfide Bond ◽  
Self Assembly ◽  
Bond Formation ◽  
Disulfide Bond Formation ◽  
Low Concentrations ◽  
Reducing Environment ◽  
Self Assembled

We report that crosslinking a self-assembled, camptothecin nanotube via disulfide bond formation reversibly stabilizes the nanotubes at low concentrations and inhibits the release of CPT. In a reducing environment, the nanotubes dissociate leading to rapid drug release.

scholarly journals Mutations in Cytochrome Assembly and Periplasmic Redox Pathways in Bordetella pertussis

2005 ◽  
Vol 187 (12) ◽  
pp. 3941-3949 ◽  
Author(s):  
Robert E. Feissner ◽  
Caroline S. Beckett ◽  
Jennifer A. Loughman ◽  
Robert G. Kranz
Keyword(s):  
Alkaline Phosphatase ◽  
Disulfide Bond ◽  
Bordetella Pertussis ◽  
Biosynthetic Pathway ◽  
Bond Formation ◽  
Disulfide Bond Formation ◽  
Entire System ◽  
Wild Type ◽  
Reducing Environment ◽  
Made In

ABSTRACT Transposon mutagenesis of Bordetella pertussis was used to discover mutations in the cytochrome c biogenesis pathway called system II. Using a tetramethyl-p-phenylenediamine cytochrome c oxidase screen, 27 oxidase-negative mutants were isolated and characterized. Nine mutants were still able to synthesize c-type cytochromes and possessed insertions in the genes for cytochrome c oxidase subunits (ctaC, -D, and -E), heme a biosynthesis (ctaB), assembly of cytochrome c oxidase (sco2), or ferrochelatase (hemZ). Eighteen mutants were unable to synthesize all c-type cytochromes. Seven of these had transposons in dipZ (dsbD), encoding the transmembrane thioreduction protein, and all seven mutants were corrected for cytochrome c assembly by exogenous dithiothreitol, which was consistent with the cytochrome c cysteinyl residues of the CXXCH motif requiring periplasmic reduction. The remaining 11 insertions were located in the ccsBA operon, suggesting that with the appropriate thiol-reducing environment, the CcsB and CcsA proteins comprise the entire system II biosynthetic pathway. Antiserum to CcsB was used to show that CcsB is absent in ccsA mutants, providing evidence for a stable CcsA-CcsB complex. No mutations were found in the genes necessary for disulfide bond formation (dsbA or dsbB). To examine whether the periplasmic disulfide bond pathway is required for cytochrome c biogenesis in B. pertussis, a targeted knockout was made in dsbB. The DsbB− mutant makes holocytochromes c like the wild type does and secretes and assembles the active periplasmic alkaline phosphatase. A dipZ mutant is not corrected by a dsbB mutation. Alternative mechanisms to oxidize disulfides in B. pertussis are analyzed and discussed.

scholarly journals Role of the Intramolecular Disulfide Bond in FlgI, the Flagellar P-Ring Component of Escherichia coli

2006 ◽  
Vol 188 (12) ◽  
pp. 4190-4197 ◽  
Author(s):  
Yohei Hizukuri ◽  
Toshiharu Yakushi ◽  
Ikuro Kawagishi ◽  
Michio Homma
Keyword(s):  
Escherichia Coli ◽  
Disulfide Bond ◽  
Self Assembly ◽  
Bacterial Species ◽  
Bond Formation ◽  
Disulfide Bond Formation ◽  
Wild Type ◽  
Ring Assembly ◽  
Intramolecular Disulfide Bond

ABSTRACT The P ring of the bacterial flagellar motor consists of multiple copies of FlgI, a periplasmic protein. The intramolecular disulfide bond in FlgI has previously been reported to be essential for P-ring assembly in Escherichia coli, because the P ring was not assembled in a dsbB strain that was defective for disulfide bond formation in periplasmic proteins. We, however, found that the two Cys residues of FlgI are not conserved in other bacterial species. We then assessed the role of this intramolecular disulfide bond in FlgI. A Cys-eliminated FlgI derivative formed a P ring that complemented the flagellation defect of our ΔflgI strain when it was overproduced, suggesting that disulfide bond formation in FlgI is not absolutely required for P-ring assembly. The levels of the mature forms of the FlgI derivatives were significantly lower than that of wild-type FlgI, although the precursor protein levels were unchanged. Moreover, the FlgI derivatives were more susceptible to degradation than wild-type FlgI. Overproduction of FlgI suppressed the motility defect of ΔdsbB cells. Additionally, the low level of FlgI observed in the ΔdsbB strain increased in the presence of l-cystine, an oxidative agent. We propose that intramolecular disulfide bond formation facilitates the rapid folding of the FlgI monomer to protect against degradation in the periplasmic space, thereby allowing its efficient self-assembly into the P ring.

scholarly journals Oxygen-independent disulfide bond formation in VEGF-A and CA9

2021 ◽  
pp. 100505
Author(s):  
Fiana Levitin ◽  
Sandy Che-Eun Serena Lee ◽  
Stephanie Hulme ◽  
Ryan A. Rumantir ◽  
Amy S. Wong ◽  
...  
Keyword(s):  
Disulfide Bond ◽  
Bond Formation ◽  
Disulfide Bond Formation

scholarly journals The Sex Differences in Uveal Melanoma: Potential Roles of EIF1AX, Immune Response and Redox Regulation

2021 ◽  
Vol 28 (4) ◽  
pp. 2801-2811
Author(s):  
Feng Liu-Smith ◽  
Chi-Yang Chiu ◽  
Daniel L. Johnson ◽  
Phillip Winston Miller ◽  
Evan S. Glazer ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Sex Difference ◽  
Uveal Melanoma ◽  
Disulfide Bond ◽  
Bond Formation ◽  
Disulfide Bond Formation ◽  
Men And Women ◽  
Copy Numbers ◽  
Differential Gene

Background: Uveal melanoma (UVM) is a rare cancer that shows sex difference in incidence and survival, with little previous report for the underlying mechanism. Methods: This study used the SEER data (1974–2016) for an age-dependent analysis on sex difference in UVM, and further used the TCGA-UVM genomics dataset for analyzing the differential gene expression profiles in tumors from men and women. Results: Our results demonstrate a sex difference in older age (≥40 years) but not in younger patients, with men exhibiting a higher incidence rate than women. However, younger women have shown a continuous increasing trend since 1974. Examining the 11 major oncogenes and tumor suppressors in UVM revealed that EIF1AX showed a significant sex difference in mRNA accumulation and copy number variation, with female tumors expressing higher levels of EIF1AX and exhibiting more variations in copy numbers. EIF1AX mRNA levels were significantly inversely correlated with EIF1AX copy numbers in female tumors only, but not in male tumors. Differential gene expression analysis at the whole genomic level identified a set of 92 protein-coding and 16 RNA-coding genes which exhibited differential expression in men and women (fold of change cutoff at 1.7, adjusted p value < 0.05, FDR < 0.05). Network analysis showed significant difference in immune response and in disulfide bond formation, with EGR1/EGR2 and PDIA2 genes as regulators for immune response and disulfide bond formation, respectively. The melanocortin pathway which is linked to both melanin synthesis and obesity seems to be altered with unclear significance, as the sex difference in POMC, DCT/TYRP2, and MRAP2 was observed but with no clear direction. Conclusion: This study reveals possible mechanisms for the sex difference in tumorigenesis of UVM which has potentials for better understanding and prevention of UVM.

scholarly journals New insights into the disulfide bond formation enzymes in epidithiodiketopiperazine alkaloids

2021 ◽  
Vol 12 (11) ◽  
pp. 4132-4138
Author(s):  
Huan Liu ◽  
Jie Fan ◽  
Peng Zhang ◽  
Youcai Hu ◽  
Xingzhong Liu ◽  
...  
Keyword(s):  
Disulfide Bond ◽  
Bond Formation ◽  
Disulfide Bond Formation ◽  
Disulfide Formation

A FAD-dependent oxidoreductase TdaR was responsible for α, β-disulfide formation in the biosynthesis of pretrichodermamide A. TdaR, together with its homologs AclT and GliT, catalysed not only α, α- but also α, β-disulfide formation in fungi.

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