id	author	title	date	pages	extension	mime	words	sentences	flesch	summary	cache	txt
cord-281597-x53ni6q1	Chiasson, Melissa A	Multiplexed measurement of variant abundance and activity reveals VKOR topology, active site and human variant impact	2020-09-01		.txt	text/plain	10185	536	54	Here, we used multiplexed, sequencing-based assays to measure the effects of 2,695 VKOR missense variants on abundance and 697 variants on activity in cultured human cells. Finally, 25% of human VKOR missense variants show reduced abundance or activity, possibly conferring warfarin sensitivity or causing disease. To understand the effect of human variants and to define the vitamin K and warfarin binding sites, VKOR variant activity has been extensively studied in cell-based assays (Czogalla et al., 2017; Shen et al., 2017; Tie et al., 2013) . We recombined a library of VKORC1 variants into the HEK293 activity reporter cell line and sorted recombinant cells into quartile bins based on carboxylation-specific antibody binding. Using these contacts, we computationally folded human VKOR, yielding a modeled structure similar to the bacterial structure (RMSD = 2.58 Å over 97/143 C alpha , Figure 3 Comparison of our abundance data to the energy required to insert different amino acids into the membrane yielded additional evidence for the four transmembrane domain model.	./cache/cord-281597-x53ni6q1.txt	./txt/cord-281597-x53ni6q1.txt