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div. section text # proj. length # Ann.
0 TIAB Structures of DPAGT1 Explain Glycosylation Disease Mechanisms and Advance TB Antibiotic Design Summa 1 1123 230 show
1 Introduction N-glycosylation of asparagine residues is a common post-translational modification of eukaryotic pro 1 3542 0 show
2 Results DPAGT1 Activity and Architecture To determine the structure of DPAGT1, we expressed both full-length 1 4866 0 show
3 Results Binding Mode for UDP-GlcNAc and Metal Ion The structure of the DPAGT1/UDP-GlcNAc complex reveals an 1 3520 0 show
4 Results Comparison of the UDP-GlcNAc and Tunicamycin Complexes The structure of the complex between tunicamy 1 1361 0 show
5 Results The DPAGT1 Catalytic Mechanism Alternative mechanisms have been proposed for the PNPT family includi 1 3905 0 show
6 Results Mutations in DPAGT1 in CMS and CDG DPAGT1-CMS and CDG-Ij are recessive disorders, caused by loss of 1 4937 0 show
7 Results Development of Non-toxic “TUN-X,X” Analogues of Tunicamycin The potent “off-target” inhibitory effec 1 2287 0 show
8 Results TUN Analogues Show Potent Antimicrobial Activity against a Range of Bacteria We evaluated the analog 1 3534 0 show
9 Results Lipid-altered TUN-X,X Analogues are Non-toxic to Eukaryotic Cells We evaluated the effect of TUN-7,7 1 4031 0 show
10 Results Lipid-altered TUN-X,Xs Show Efficacy against Mtb in Mice The enhanced therapeutic index of the TUN-X 1 1926 0 show
11 Discussion Structures of DPAGT1 allowed us to explain the mechanism of this key enzyme in protein N-glycosylati 1 3118 0 show
12 STAR★Methods Key Resources Table 1 19 0 show
13 STAR★Methods Contact for Reagent and Resource Sharing Further information and requests for resources and reagents 1 209 0 show
14 STAR★Methods Experimental Model and Subject Details Bacteria The strain and source of all the bacteria used in th 1 2388 0 show
15 STAR★Methods Method Details Cloning and expression The WT DPAGT1 cDNA sequence was cloned into the pFB-LIC-Bse ex 1 38071 0 show
16 STAR★Methods Quantification and Statistical Analysis All values are the mean ± standard deviation. GraphPad Prism 1 224 0 show
17 STAR★Methods Data and Software Availability The crystal structures presented in this paper have been deposited in 1 245 0 show
18 Caption-Figure 1 Structural Features of DPAGT1 (A) Cartoon of DPAGT1 reaction. (B) Michaelis-Menten kinetics, non-tit 1 605 0 show
19 Caption-Figure S1 Biochemical and Biophysical Characterization of DPAGT1, Related to Figure 1 (A) Cartoon of DPAGT1 sh 1 1325 0 show
20 Caption-Figure S2 Electron Density Maps, Heavy Atom Phasing and Dimer Interface Analysis for the Structure of Dimeric 1 2583 0 show
21 Caption-Figure 2 DPAGT1 Active Site (A) The loops that form the active site; UDP-GlcNAc in magenta. (B) Sliced molecu 1 942 0 show
22 Caption-Figure 3 Proposed DPAGT1 Catalytic Mechanism (A) Relative activity of active site mutant residues; (n=9). (B) 1 300 0 show
23 Caption-Figure 4 DPAGT1 CMS and CDG-Ij Missense Variants Analyses (A) Relative activity and (B) thermostability for D 1 1055 0 show
24 Caption-Figure S3 The c.478G>A; Gly160Ser and c.791T>G; Val264Gly Mutations Are Associated with Exon Splicing Errors, 1 1568 0 show
25 Caption-Figure 5 Semi-synthetic Synthesis and Antibacterial Effects of TUN-X,X Analogues (A) Semi-synthetic strategy 1 381 0 show
26 Caption-Figure S4 Kirby-Bauer Disc Diffusion Tests and Dose Response Curves Used for MIC, MBC, and IC50 Determination 1 1289 0 show
27 Caption-Figure S5 On-Target Effects Demonstrated for the TUN-8,8 Analogue, Related to Figure 5 (A) Glucosamine incorpo 1 907 0 show
28 Caption-Figure 6 TUN-X,X Analogues are Not Toxic to Cultured Human Cells (A–C) Dose response curves from cell prolife 1 757 0 show
29 Caption-Figure S6 Effect of Tunicamycin and Analogues on HEK293 Cells, Related to Figure 6 (A) Cell cycle analysis at 1 385 0 show
30 Caption-Figure 7 Tunicamycin Analogues Eradicate Mtb during Host Pathogenesis (A) Efficacy of tunicamycin analogues i 1 1043 0 show