ArticlePloS one2011
Histidine hydrogen-deuterium exchange mass spectrometry for probing the microenvironment of histidine residues in dihydrofolate reductase.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 31 citations in OpenAlex.
- Advancing Structural Biology and Protein-Ligand Interactions through Hydrogen/Deuterium Exchange Mass Spectrometry (HDX-MS).Methods in molecular biology (Clifton, N.J.) · 2025Article
- Solution Ionic Strength Can Modulate Functional Loop Conformations inThe journal of physical chemistry. B · 2024Article
- Significance of Histidine Hydrogen-Deuterium Exchange Mass Spectrometry in Protein Structural Biology.Biology · 2024Review
- Advances in Hydrogen/Deuterium Exchange Mass Spectrometry and the Pursuit of Challenging Biological Systems.Chemical reviews · 2022Review
- Structurally distinct external solvent-exposed domains drive replication of major human prions.PLoS pathogens · 2021Article
- Article
- Revisiting the pH-gated conformational switch on the activities of HisKA-family histidine kinases.Nature communications · 2020Article
- Stable Deuterium Labeling of Histidine-Rich Lysine-Based Dendrimers.Molecules (Basel, Switzerland) · 2019Article
- Gas-Phase Hydrogen/Deuterium Scrambling in Negative-Ion Mode Tandem Mass Spectrometry.Journal of the American Society for Mass Spectrometry · 2019Article
- Structural attributes of mammalian prion infectivity: Insights from studies with synthetic prions.The Journal of biological chemistry · 2018Article
- Modulating Enzyme Activity by Altering Protein Dynamics with Solvent.Biochemistry · 2018Article
- Post-translational modifications in PrP expand the conformational diversity of prions in vivo.Scientific reports · 2017Article
- Determination of Histidine pKa Values in the Propeptides of Furin and Proprotein Convertase 1/3 Using Histidine Hydrogen-Deuterium Exchange Mass Spectrometry.Analytical chemistry · 2015Article
- Structural determinants of phenotypic diversity and replication rate of human prions.PLoS pathogens · 2015Article
- Long-range stabilization of anthrax protective antigen upon binding to CMG2.Biochemistry · 2014Article
- Conformational stability of mammalian prion protein amyloid fibrils is dictated by a packing polymorphism within the core region.The Journal of biological chemistry · 2014Article
- Identifying Zn-bound histidine residues in metalloproteins using hydrogen-deuterium exchange mass spectrometry.Analytical chemistry · 2014Article
- Quantitative measurement of the solvent accessibility of histidine imidazole groups in proteins.Biochemistry · 2012Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
backgroundHistidine Hydrogen-Deuterium Exchange Mass Spectrometry (His-HDX-MS) determines the HDX rates at the imidazole C(2)-hydrogen of histidine residues. This method provides not only the HDX rates but also the pK(a) values of histidine imidazole rings. His-HDX-MS was used to probe the microenvironment of histidine residues of E. coli dihydrofolate reductase (DHFR), an enzyme proposed to undergo multiple conformational changes during catalysis. METHODOLOGY/PRINCIPAL
findingsUsing His-HDX-MS, the pK(a) values and the half-lives (t(1/2)) of HDX reactions of five histidine residues of apo-DHFR, DHFR in complex with methotrexate (DHFR-MTX), DHFR in complex with MTX and NADPH (DHFR-MTX-NADPH), and DHFR in complex with folate and NADP+ (DHFR-folate-NADP+) were determined. The results showed that the two parameters (pK(a) and t(1/2)) are sensitive to the changes of the microenvironment around the histidine residues. Although four of the five histidine residues are located far from the active site, ligand binding affected their pK(a), t(1/2) or both. This is consistent with previous observations of ligand binding-induced distal conformational changes on DHFR. Most of the observed pK(a) and t(1/2) changes could be rationalized using the X-ray structures of apo-DHFR, DHFR-MTX-NADPH, and DHFR-folate-NADP+. The availability of the neutron diffraction structure of DHFR-MTX enabled us to compare the protonation states of histidine imidazole rings. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate the usefulness of His-HDX-MS in probing the microenvironments of histidine residues within proteins.
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