ArticleNucleic acids research2008
Molecular basis for the lack of enantioselectivity of human 3-phosphoglycerate kinase.
Article in Nucleic acids research, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 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
17 citing papers in PubMed, 38 citations in OpenAlex.
- Chemoproteomic Profiling Maps Zinc-Dependent Cysteine Reactivity.Chemical research in toxicology · 2024Article
- Exploring the association between serum phosphate levels and mortality in patients hospitalized with infectious diseases: a nationwide study.Frontiers in medicine · 2024Article
- Targeting phosphoglycerate kinases by tatridin A, a natural sesquiterpenoid endowed with anti-cancer activity, using a proteomic platform.Frontiers in molecular biosciences · 2023Article
- Loss of stability and unfolding cooperativity in hPGK1 upon gradual structural perturbation of its N-terminal domain hydrophobic core.Scientific reports · 2022Article
- The Discovery of Novel PGK1 Activators as Apoptotic Inhibiting and Neuroprotective Agents.Frontiers in pharmacology · 2022Article
- Molecular mechanism of glycolytic flux control intrinsic to human phosphoglycerate kinase.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- A Novel Pyrazolopyrimidine Ligand of Human PGK1 and Stress Sensor DJ1 Modulates the Shelterin Complex and Telomere Length Regulation.Neoplasia (New York, N.Y.) · 2019Article
- Cryo-EM fibril structures from systemic AA amyloidosis reveal the species complementarity of pathological amyloids.Nature communications · 2019Article
- NTyroSite: Computational Identification of Protein Nitrotyrosine Sites Using Sequence Evolutionary Features.Molecules (Basel, Switzerland) · 2018Article
- Article
- Virtual Screening against Phosphoglycerate Kinase 1 in Quest of Novel Apoptosis Inhibitors.Molecules (Basel, Switzerland) · 2017Article
- Protein Stability, Folding and Misfolding in Human PGK1 Deficiency.Biomolecules · 2013Article
- Mechanisms of protein sequence divergence and incompatibility.PLoS genetics · 2013Article
- Transient kinetics of aminoglycoside phosphotransferase(3')-IIIa reveals a potential drug target in the antibiotic resistance mechanism.FEBS letters · 2012Article
- Crystal structures of putative phosphoglycerate kinases from B. anthracis and C. jejuni.Journal of structural and functional genomics · 2012Article
- Molecular insights on pathogenic effects of mutations causing phosphoglycerate kinase deficiency.PloS one · 2012Article
- A spring-loaded release mechanism regulates domain movement and catalysis in phosphoglycerate kinase.The Journal of biological chemistry · 2011Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Non-natural L-nucleoside analogues are increasingly used as therapeutic agents to treat cancer and viral infections. To be active, L-nucleosides need to be phosphorylated to their respective triphosphate metabolites. This stepwise phosphorylation relies on human enzymes capable of processing L-nucleoside enantiomers. We used crystallographic analysis to reveal the molecular basis for the low enantioselectivity and the broad specificity of human 3-phosphoglycerate kinase (hPGK), an enzyme responsible for the last step of phosphorylation of many nucleotide derivatives. Based on structures of hPGK in the absence of nucleotides, and bound to L and d forms of MgADP and MgCDP, we show that a non-specific hydrophobic clamp to the nucleotide base, as well as a water-filled cavity behind it, allows high flexibility in the interaction between PGK and the bases. This, combined with the dispensability of hydrogen bonds to the sugar moiety, and ionic interactions with the phosphate groups, results in the positioning of different nucleotides so to expose their diphosphate group in a position competent for catalysis. Since the third phosphorylation step is often rate limiting, our results are expected to alleviate in silico tailoring of L-type prodrugs to assure their efficient metabolic processing.
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.