ArticleAngewandte Chemie (International ed. in English)2015
Kinetic Cooperativity in Human Pancreatic Glucokinase Originates from Millisecond Dynamics of the Small Domain.
Article in Angewandte Chemie (International ed. in English), 2015. 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, 38 citations in OpenAlex.
- Characterizing glucokinase variant mechanisms using a multiplexed abundance assay.Genome biology · 2024Article
- A comprehensive map of human glucokinase variant activity.Genome biology · 2023Article
- Biochemical methods to map and quantify allosteric motions in human glucokinase.Methods in enzymology · 2023Article
- Moonlighting Proteins: The Case of the Hexokinases.Frontiers in molecular biosciences · 2021Review
- Nanosecond-Timescale Dynamics and Conformational Heterogeneity in Human GCK Regulation and Disease.Biophysical journal · 2020Article
- Reducing Glucokinase Activity to Enhance Insulin Secretion: A Counterintuitive Theory to Preserve Cellular Function and Glucose Homeostasis.Frontiers in endocrinology · 2020Article
- Propagation of the Allosteric Signal in Phosphofructokinase fromBiochemistry · 2019Article
- Nitric Oxide Activates β-Cell Glucokinase by Promoting Formation of the "Glucose-Activated" State.Biochemistry · 2018Article
- Mechanistic Origins of Enzyme Activation in Human Glucokinase Variants Associated with Congenital Hyperinsulinism.Biochemistry · 2018Article
- Evidence-based tailoring of bioinformatics approaches to optimize methods that predict the effects of nonsynonymous amino acid substitutions in glucokinase.Scientific reports · 2017Article
- Residue-Specific Interactions of an Intrinsically Disordered Protein with Silica Nanoparticles and their Quantitative Prediction.The journal of physical chemistry. C, Nanomaterials and interfaces · 2016Article
- Role of Proteome Physical Chemistry in Cell Behavior.The journal of physical chemistry. B · 2016Review
- Solution NMR Spectroscopy for the Study of Enzyme Allostery.Chemical reviews · 2016Review
- NMR Methods to Study Dynamic Allostery.PLoS computational biology · 2016Review
- Dual allosteric activation mechanisms in monomeric human glucokinase.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Small Molecule Targeting of Protein-Protein Interactions through Allosteric Modulation of Dynamics.Molecules (Basel, Switzerland) · 2015Review
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 4 institutions in 1 country.
Funding
Abstract
The hallmark of glucokinase (GCK), which catalyzes the phosphorylation of glucose during glycolysis, is its kinetic cooperativity, whose understanding at atomic detail has remained open since its discovery over 40 years ago. Herein, by using kinetic CPMG NMR spectroscopic data for 17 isoleucine side chains distributed over all parts of GCK, we show that the origin of kinetic cooperativity is rooted in intramolecular protein dynamics. Residues of glucose-free GCK located in the small domain displayed distinct exchange behavior involving multiple conformers that are substantially populated (p>17 %) with a kex value of 509±51 s(-1) , whereas in the glucose-bound form these exchange processes were quenched. This exchange behavior directly competes with the enzymatic turnover rate at physiological glucose concentrations, thereby generating the sigmoidal rate dependence that defines kinetic cooperativity.
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.