ArticleBiochemistry2011
Comparative hydrogen-deuterium exchange for a mesophilic vs thermophilic dihydrofolate reductase at 25 °C: identification of a single active site region with enhanced flexibility in the mesophilic protein.
Article in Biochemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 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
16 citing papers in PubMed, 26 citations in OpenAlex.
- Article
- Site-resolved energetic information from HX-MS experiments.Nature chemical biology · 2026Article
- Hydrogen-Deuterium Exchange within Adenosine Deaminase, a TIM Barrel Hydrolase, Identifies Networks for Thermal Activation of Catalysis.Journal of the American Chemical Society · 2020Article
- Quantifying the Relationship between Conformational Dynamics and Enzymatic Activity in Ribonuclease HI Homologues.Biochemistry · 2020Article
- Electric Field Measurements Reveal the Pivotal Role of Cofactor-Substrate Interaction in Dihydrofolate Reductase Catalysis.ACS catalysis · 2020Article
- Hydrogen deuterium exchange defines catalytically linked regions of protein flexibility in the catecholProceedings of the National Academy of Sciences of the United States of America · 2020Article
- A temperature-dependent conformational shift in p38α MAPK substrate-binding region associated with changes in substrate phosphorylation profile.The Journal of biological chemistry · 2019Article
- Enzymatic Kinetic Isotope Effects from Path-Integral Free Energy Perturbation Theory.Methods in enzymology · 2016Article
- Structural Rigidity and Protein Thermostability in Variants of Lipase A from Bacillus subtilis.PloS one · 2015Article
- Thermal adaptation of dihydrofolate reductase from the moderate thermophile Geobacillus stearothermophilus.Biochemistry · 2014Article
- Hydrogen tunneling in enzymes and biomimetic models.Chemical reviews · 2014Review
- Identification of a long-range protein network that modulates active site dynamics in extremophilic alcohol dehydrogenases.The Journal of biological chemistry · 2013Article
- Connecting protein conformational dynamics with catalytic function as illustrated in dihydrofolate reductase.Biochemistry · 2013Article
- Multiple intermediates, diverse conformations, and cooperative conformational changes underlie the catalytic hydride transfer reaction of dihydrofolate reductase.Topics in current chemistry · 2013Review
- Thermal adaptation of conformational dynamics in ribonuclease H.PLoS computational biology · 2013Article
- Hydrogen tunneling links protein dynamics to enzyme catalysis.Annual review of biochemistry · 2013Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
The technique of hydrogen-deuterium exchange coupled to mass spectrometry (HDX-MS) has been applied to a mesophilic (E. coli) dihydrofolate reductase under conditions that allow direct comparison to a thermophilic (B. stearothermophilus) ortholog, Ec-DHFR and Bs-DHFR, respectively. The analysis of hydrogen-deuterium exchange patterns within proteolytically derived peptides allows spatial resolution, while requiring a series of controls to compare orthologous proteins with only ca. 40% sequence identity. These controls include the determination of primary structure effects on intrinsic rate constants for HDX as well as the use of existing 3-dimensional structures to evaluate the distance of each backbone amide hydrogen to the protein surface. Only a single peptide from the Ec-DHFR is found to be substantially more flexible than the Bs-DHFR at 25 °C in a region located within the protein interior at the intersection of the cofactor and substrate-binding sites. The surrounding regions of the enzyme are either unchanged or more flexible in the thermophilic DHFR from B. stearothermophilus. The region with increased flexibility in Ec-DHFR corresponds to one of two regions previously proposed to control the enthalpic barrier for hydride transfer in Bs-DHFR [Oyeyemi et al. (2010) Proc. Natl. Acad. Sci. U.S.A. 107, 10074].
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.