ArticleProtein science : a publication of the Protein Society2015
Impact of cysteine variants on the structure, activity, and stability of recombinant human α-galactosidase A.
Article in Protein science : a publication of the Protein Society, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 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
15 citing papers in PubMed, 37 citations in OpenAlex.
- In Silico Characterization of PathogenicGenes · 2025Article
- Insight into improved specificity and thermostability of3 Biotech · 2025Article
- Molecular Dynamic Study on the Structure and Thermal Stability of Mutant Pediocin PA-1 Peptides Engineered with Cysteine Substitutions.Probiotics and antimicrobial proteins · 2025Article
- Case Report: Novel GLA mutation in a Chinese female with renal-predominant Fabry disease and cardiac hypertrophy.Frontiers in genetics · 2025Article
- Effect of Free Cysteine Residues to Serine Mutation on Cellodextrin Phosphorylase.Journal of applied glycoscience · 2024Article
- Optimizing human α-galactosidase for treatment of Fabry disease.Scientific reports · 2023Article
- Cysteine Pathogenic Variants of PMM2 Are Sensitive to Environmental Stress with Loss of Structural Stability.Oxidative medicine and cellular longevity · 2023Article
- Analyzing protein posttranslational modifications using enzyme-catalyzed expressed protein ligation.Methods in enzymology · 2023Article
- Roles of cysteine in the structure and metabolic function ofRSC advances · 2022Article
- Beyond structure: Deciphering site-specific dynamics in proteins from double histidine-based EPR measurements.Protein science : a publication of the Protein Society · 2022Article
- Molecular dissection of a dedicated formaldehyde dehydrogenase from Mycobacterium smegmatis.Protein science : a publication of the Protein Society · 2022Article
- Copper Based Site-directed Spin Labeling of Proteins for Use in Pulsed and Continuous Wave EPR Spectroscopy.Bio-protocol · 2021Article
- Human α-Galactosidase A Mutants: Priceless Tools to Develop Novel Therapies for Fabry Disease.International journal of molecular sciences · 2021Review
- Thiol Redox Regulation of Plant β-Carbonic Anhydrase.Biomolecules · 2020Article
- Insight into Improved Thermostability of Cold-Adapted Staphylococcal Lipase by Glycine to Cysteine Mutation.Molecules (Basel, Switzerland) · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Recombinant human α-galactosidase A (rhαGal) is a homodimeric glycoprotein deficient in Fabry disease, a lysosomal storage disorder. In this study, each cysteine residue in rhαGal was replaced with serine to understand the role each cysteine plays in the enzyme structure, function, and stability. Conditioned media from transfected HEK293 cells were assayed for rhαGal expression and enzymatic activity. Activity was only detected in the wild type control and in mutants substituting the free cysteine residues (C90S, C174S, and the C90S/C174S). Cysteine-to-serine substitutions at the other sites lead to the loss of expression and/or activity, consistent with their involvement in the disulfide bonds found in the crystal structure. Purification and further characterization confirmed that the C90S, C174S, and the C90S/C174S mutants are enzymatically active, structurally intact and thermodynamically stable as measured by circular dichroism and thermal denaturation. The purified inactive C142S mutant appeared to have lost part of its alpha-helix secondary structure and had a lower apparent melting temperature. Saturation mutagenesis study on Cys90 and Cys174 resulted in partial loss of activity for Cys174 mutants but multiple mutants at Cys90 with up to 87% higher enzymatic activity (C90T) compared to wild type, suggesting that the two free cysteines play differential roles and that the activity of the enzyme can be modulated by side chain interactions of the free Cys residues. These results enhanced our understanding of rhαGal structure and function, particularly the critical roles that cysteines play in structure, stability, and enzymatic activity.
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.