{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Takeuchi K"],"funding":["NCI NIH HHS","NINDS NIH HHS"],"pagination":["886-899.e4"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9177683"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["30(6)"],"pubmed_abstract":["Unlike most kinases, phosphatidylinositol 5-phosphate 4-kinase β (PI5P4Kβ) utilizes GTP as a physiological phosphate donor and regulates cell growth under stress (i.e., GTP-dependent stress resilience). However, the genesis and evolution of its GTP responsiveness remain unknown. Here, we reveal that PI5P4Kβ has acquired GTP preference by generating a short dual-nucleotide-recognizing motif called the guanine efficient association (GEA) motif. Comparison of nucleobase recognition with 660 kinases and 128 G proteins has uncovered that most kinases and PI5P4Kβ use their main-chain atoms for adenine recognition, while the side-chain atoms are required for guanine recognition. Mutational analysis of the GEA motif revealed that the acquisition of GTP reactivity is accompanied by an extended acti"],"journal":["Structure (London, England : 1993)"],"pubmed_title":["The GTP responsiveness of PI5P4Kβ evolved from a compromised trade-off between activity and specificity."],"pmcid":["PMC9177683"],"funding_grant_id":["R01 NS089815","R01 CA255331","R21 NS100077"],"pubmed_authors":["Ikeda Y","Okuwaki K","Sasaki M","Takeuchi K","Fukuzawa K","Imai M","Nagase L","Lo YH","Yu HY","Sasaki AT","Ito D","Osaka N","Fujii Y","Senda T","Harada A","Nakagawa S","Senda M"],"additional_accession":[]},"is_claimable":false,"name":"The GTP responsiveness of PI5P4Kβ evolved from a compromised trade-off between activity and specificity.","description":"Unlike most kinases, phosphatidylinositol 5-phosphate 4-kinase β (PI5P4Kβ) utilizes GTP as a physiological phosphate donor and regulates cell growth under stress (i.e., GTP-dependent stress resilience). However, the genesis and evolution of its GTP responsiveness remain unknown. Here, we reveal that PI5P4Kβ has acquired GTP preference by generating a short dual-nucleotide-recognizing motif called the guanine efficient association (GEA) motif. Comparison of nucleobase recognition with 660 kinases and 128 G proteins has uncovered that most kinases and PI5P4Kβ use their main-chain atoms for adenine recognition, while the side-chain atoms are required for guanine recognition. Mutational analysis of the GEA motif revealed that the acquisition of GTP reactivity is accompanied by an extended acti","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Jun","modification":"2026-05-09T22:15:28.423Z","creation":"2024-11-10T07:20:24.434Z"},"accession":"S-EPMC9177683","cross_references":{"pubmed":["35504278"],"doi":["10.1016/j.str.2022.04.004"]}}