ArticleThe Journal of biological chemistry2012
Structural studies and protein engineering of inositol phosphate multikinase.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 37 citations in OpenAlex.
- Structural insights into the development of inhibitors for inositol phosphate kinases.FEBS letters · 2026Review
- Structural Rationalization of IPMK Inhibitor Potency.Journal of medicinal chemistry · 2025Article
- Design, Synthesis, and Cellular Characterization of a New Class of IPMK Kinase Inhibitors.Journal of medicinal chemistry · 2025Article
- Article
- Inositol Phosphate Kinase Architecture: Practical Approaches and Lessons Learned.Methods in molecular biology (Clifton, N.J.) · 2025Review
- Origin, evolution, and diversification of inositol 1,4,5-trisphosphate 3-kinases in plants and animals.BMC genomics · 2024Article
- Review
- Rice EARLY SENESCENCE 2, encoding an inositol polyphosphate kinase, is involved in leaf senescence.BMC plant biology · 2020Article
- Direct Activation of Human MLKL by a Select Repertoire of Inositol Phosphate Metabolites.Cell chemical biology · 2019Article
- Signaling through non-membrane nuclear phosphoinositide binding proteins in human health and disease.Journal of lipid research · 2019Review
- Inositol phosphate kinases: Expanding the biological significance of the universal core of the protein kinase fold.Advances in biological regulation · 2019Review
- Crystallographic and kinetic analyses of human IPMK reveal disordered domains modulate ATP binding and kinase activity.Scientific reports · 2018Article
- Inositol polyphosphate multikinase regulation of Trypanosoma brucei life stage development.Molecular biology of the cell · 2018Article
- Arabidopsis inositol polyphosphate multikinase delays flowering time through mediating transcriptional activation of FLOWERING LOCUS C.Journal of experimental botany · 2017Article
- Structural features of human inositol phosphate multikinase rationalize its inositol phosphate kinase and phosphoinositide 3-kinase activities.The Journal of biological chemistry · 2017Article
- Inositol phosphate multikinase dependent transcriptional control.Advances in biological regulation · 2017Article
- Inositol Polyphosphate Kinases, Fungal Virulence and Drug Discovery.Journal of fungi (Basel, Switzerland) · 2016Review
- Chemogenetic Characterization of Inositol Phosphate Metabolic Pathway Reveals Druggable Enzymes for Targeting Kinetoplastid Parasites.Cell chemical biology · 2016Article
- Inositol polyphosphate multikinase (IPMK) in transcriptional regulation and nuclear inositide metabolism.Biochemical Society transactions · 2016Review
- A High-Throughput Screening-Compatible Strategy for the Identification of Inositol Pyrophosphate Kinase Inhibitors.PloS one · 2016Article
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Inositol phosphates (IPs) regulate vital processes in eukaryotes, and their production downstream of phospholipase C activation is controlled through a network of evolutionarily conserved kinases and phosphatases. Inositol phosphate multikinase (IPMK, also called Ipk2 and Arg82) accounts for phosphorylation of IP(3) to IP(5), as well as production of several other IP molecules. Here, we report the structure of Arabidopsis thaliana IPMKα at 2.9 Å and find it is similar to the yeast homolog Ipk2, despite 17% sequence identity, as well as the active site architecture of human IP(3) 3-kinase. Structural comparison and substrate modeling were used to identify a putative basis for IPMK selectivity. To test this model, we re-engineered binding site residues predicted to have restricted substrate specificity. Using steady-state kinetics and in vivo metabolic labeling studies in modified yeast strains, we observed that K117W and K117W:K121W mutants exhibited nearly normal 6-kinase function but harbored significantly reduced 3-kinase activity. These mutants complemented conditional nutritional growth defects observed in ipmk null yeast and, remarkably, suppressed lethality observed in ipmk null flies. Our data are consistent with the hypothesis that IPMK 6-kinase activity and production of Ins(1,4,5,6)P(4) are critical for cellular signaling. Overall, our studies provide new insights into the structure and function of IPMK and utilize a synthetic biological approach to redesign inositol phosphate signaling pathways.
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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.