ArticleBiochemistry2008
Cysteine pKa depression by a protonated glutamic acid in human DJ-1.
Article in Biochemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 73 papers.
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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.
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Who cites it
73 citing papers in PubMed, 140 citations in OpenAlex.
- Crosstalk between cysteine and lysine modifications: Integrating redox and metabolic regulation.Redox biology · 2026Review
- Implementation and Validation of Titratable Cysteine in GROMACS-Based Constant-pH Molecular Dynamics.Journal of chemical theory and computation · 2026Article
- Environmental Contributions to Proton Sharing in Protein Low-Barrier Hydrogen Bonds.Biochemistry · 2026Article
- Evolution, structure and function of L-cysteine desulfidase, an enzyme involved in sulfur metabolism in the methanogenic archeon Methanococcus maripaludis.Communications biology · 2025Article
- Environmental Contributions to Proton Sharing in Protein Low-Barrier Hydrogen Bonds.bioRxiv : the preprint server for biology · 2025Article
- Discovery and Profiling of Protein CysteineMolecules (Basel, Switzerland) · 2025Article
- Combining Reactive Quantum-Mechanical Molecular-Dynamics Simulations with Mutagenesis, Crystallography, and Enzyme Kinetics to Reveal Plausible Steps of Isocyanide Hydratase Catalysis.Journal of chemical information and modeling · 2025Article
- The reaction mechanism for glycolysis side product degradation by Parkinson's disease-linked DJ-1.The Journal of cell biology · 2025Article
- CIAA: Integrated Proteomics and Structural Modeling for Understanding Cysteine Reactivity with Iodoacetamide Alkyne.ACS chemical biology · 2025Article
- Improving pJournal of chemical theory and computation · 2025Article
- Development and use of DJ-1 affinity microcolumns to screen and study small drug candidates for Parkinson's disease.Analytica chimica acta · 2025Article
- Resolving DJ-1 Glyoxalase Catalysis Using Mix-and-Inject Serial Crystallography at a Synchrotron.bioRxiv : the preprint server for biology · 2024Article
- Changes in an enzyme ensemble during catalysis observed by high-resolution XFEL crystallography.Science advances · 2024Article
- Article
- Changes in an Enzyme Ensemble During Catalysis Observed by High Resolution XFEL Crystallography.bioRxiv : the preprint server for biology · 2023Article
- Kinetic evidence in favor of glyoxalase III and against deglycase activity of DJ-1.Protein science : a publication of the Protein Society · 2023Article
- A novel splicing variant of DJ-1 in Parkinson's disease induces mitochondrial dysfunction.Heliyon · 2023Article
- Persulfidation of DJ-1: Mechanism and Consequences.Biomolecules · 2022Article
- Understanding Cysteine Chemistry Using Conventional and Serial X-Ray Protein Crystallography.Crystals · 2022Article
- Cysteine Oxidation in Proteins: Structure, Biophysics, and Simulation.Biochemistry · 2022Review
13 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Human DJ-1, a disease-associated protein that protects cells from oxidative stress, contains an oxidation-sensitive cysteine (C106) that is essential for its cytoprotective activity. The origin of C106 reactivity is obscure, due in part to the absence of an experimentally determined p K a value for this residue. We have used atomic-resolution X-ray crystallography and UV spectroscopy to show that C106 has a depressed p K a of 5.4 +/- 0.1 and that the C106 thiolate accepts a hydrogen bond from a protonated glutamic acid side chain (E18). X-ray crystal structures and cysteine p K a analysis of several site-directed substitutions at residue 18 demonstrate that the protonated carboxylic acid side chain of E18 is required for the maximal stabilization of the C106 thiolate. A nearby arginine residue (R48) participates in a guanidinium stacking interaction with R28 from the other monomer in the DJ-1 dimer and elevates the p K a of C106 by binding an anion that electrostatically suppresses thiol ionization. Our results show that the ionizable residues (E18, R48, and R28) surrounding C106 affect its p K a in a way that is contrary to expectations based on the typical ionization behavior of glutamic acid and arginine. Lastly, a search of the Protein Data Bank (PDB) produces several candidate hydrogen-bonded aspartic/glutamic acid-cysteine interactions, which we propose are particularly common in the DJ-1 superfamily.
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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.