ArticleThe Journal of biological chemistry2010
Rescue of cystathionine beta-synthase (CBS) mutants with chemical chaperones: purification and characterization of eight CBS mutant enzymes.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
43 citing papers in PubMed, 80 citations in OpenAlex.
- Structural basis for a filamentous morpheein model of human cystathionine beta-synthase.Nature communications · 2026Article
- Impact of primary sequence changes on the self-association properties of mammalian cystathionine beta-synthase enzymes.Protein science : a publication of the Protein Society · 2024Article
- Cellular turnover and degradation of the most common missense cystathionine beta-synthase variants causing homocystinuria.Protein science : a publication of the Protein Society · 2024Article
- Architecture and regulation of filamentous human cystathionine beta-synthase.Nature communications · 2024Article
- satmut_utils: a simulation and variant calling package for multiplexed assays of variant effect.Genome biology · 2023Article
- Recent therapeutic approaches to cystathionine beta-synthase-deficient homocystinuria.British journal of pharmacology · 2023Review
- Genetic and Pharmacological Modulation of Cellular Proteostasis Leads to Partial Functional Rescue of Homocystinuria-Causing Cystathionine-Beta Synthase Variants.Molecular and cellular biology · 2023Article
- Examination of two different proteasome inhibitors in reactivating mutant human cystathionine β-synthase in mice.PloS one · 2023Article
- How to fix a broken protein: restoring function to mutant human cystathionine β-synthase.Human genetics · 2022Review
- Biosynthesis, Quantification and Genetic Diseases of the Smallest Signaling Thiol Metabolite: Hydrogen Sulfide.Antioxidants (Basel, Switzerland) · 2021Review
- NovelFrontiers in pediatrics · 2021Article
- Review
- Cerebral venous sinus thrombosis due to hyperhomocysteinemia with cystathionine-β-synthase (CBS) gene mutation: A case report.Medicine · 2019Article
- Hydrogen Sulfide Biochemistry and Interplay with Other Gaseous Mediators in Mammalian Physiology.Oxidative medicine and cellular longevity · 2018Review
- A Clinically Relevant Variant of the Human Hydrogen Sulfide-Synthesizing Enzyme CystathionineOxidative medicine and cellular longevity · 2017Article
- The genetic basis of classic nonketotic hyperglycinemia due to mutations in GLDC and AMT.Genetics in medicine : official journal of the American College of Medical Genetics · 2017Article
- Chaperone therapy for homocystinuria: the rescue of CBS mutations by heme arginate.Journal of inherited metabolic disease · 2015Article
- S-glutathionylation enhances human cystathionine β-synthase activity under oxidative stress conditions.Antioxidants & redox signaling · 2015Article
- Functional characterization and categorization of missense mutations that cause methylmalonyl-CoA mutase (MUT) deficiency.Human mutation · 2014Article
- Compromised catalysis and potential folding defects in in vitro studies of missense mutants associated with hereditary phosphoglucomutase 1 deficiency.The Journal of biological chemistry · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Missense mutations represent the most common cause of many genetic diseases including cystathionine beta-synthase (CBS) deficiency. Many of these mutations result in misfolded proteins, which lack biological function. The presence of chemical chaperones can sometimes alleviate or even restore protein folding and activity of mutant proteins. We present the purification and characterization of eight CBS mutants expressed in the presence of chemical chaperones such as ethanol, dimethyl sulfoxide, or trimethylamine-N-oxide. Preliminary screening in Escherichia coli crude extracts showed that their presence during protein expression had a significant impact on the amount of recovered CBS protein, formation of tetramers, and catalytic activity. Subsequently, we purified eight CBS mutants to homogeneity (P49L, P78R, A114V, R125Q, E176K, P422L, I435T, and S466L). The tetrameric mutant enzymes fully saturated with heme had the same or higher specific activities than wild type CBS. Thermal stability measurements demonstrated that the purified mutants are equally or more thermostable than wild type CBS. The response to S-adenosyl-L-methionine stimulation or thermal activation varied. The lack of response of R125Q and E176K to both stimuli indicated that their specific conformations were unable to reach the activated state. Increased levels of molecular chaperones in crude extracts, particularly DnaJ, indicated a rather indirect effect of the chemical chaperones on folding of CBS mutants. In conclusion, the chemical chaperones present in the expression medium were able to fully restore the activity of eight CBS mutants by improving their protein folding. This finding could have direct implications for the development of a therapeutical approach to pyridoxine unresponsive homocystinuria.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.