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- W4377965889 abstract "Amino acid substitutions can perturb protein activity in multiple ways. Understanding their mechanistic basis may pinpoint how residues contribute to protein function. Here, we characterize the mechanisms of human glucokinase (GCK) variants, building on our previous comprehensive study on GCK variant activity. We assayed the abundance of 95% of GCK missense and nonsense variants, and found that 43% of hypoactive variants have a decreased cellular abundance. By combining our abundance scores with predictions of protein thermodynamic stability, we identify residues important for GCK metabolic stability and conformational dynamics. These residues could be targeted to modulate GCK activity, and thereby affect glucose homeostasis." @default.
- W4377965889 created "2023-05-25" @default.
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- W4377965889 date "2023-05-24" @default.
- W4377965889 modified "2023-09-29" @default.
- W4377965889 title "Characterizing glucokinase variant mechanisms using a multiplexed abundance assay" @default.
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- W4377965889 doi "https://doi.org/10.1101/2023.05.24.542036" @default.
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