5lev

Crystal structure of human UDP-N-acetylglucosamine-dolichyl-phosphate N-acetylglucosaminephosphotransferase (DPAGT1) (V264G mutant)

spinqualitylabelsall models 5lev, resolution 3.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5lev is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.2Å Ligands: UNL Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease GPT_HUMAN DPAGT1-CDG;Congenital myasthenic syndromes with glycosylation defect. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. Function GPT_HUMAN Catalyzes the initial step in the synthesis of dolichol-P-P-oligosaccharides. Publication Abstract from PubMed Protein N-glycosylation is a widespread post-translational modification. The first committed step in this process is catalysed by dolichyl-phosphate N-acetylglucosamine-phosphotransferase DPAGT1 (GPT/E.C. 2.7.8.15). Missense DPAGT1 variants cause congenital myasthenic syndrome and disorders of glycosylation. In addition, naturally-occurring bactericidal nucleoside analogues such as tunicamycin are toxic to eukaryotes due to DPAGT1 inhibition, preventing their clinical use. Our structures of DPAGT1 with the substrate UDP-GlcNAc and tunicamycin reveal substrate binding modes, suggest a mechanism of catalysis, provide an understanding of how mutations modulate activity (thus causing disease) and allow design of non-toxic "lipid-altered" tunicamycins. The structure-tuned activity of these analogues against several bacterial targets allowed the design of potent antibiotics for Mycobacterium tuberculosis, enabling treatment in vitro, in cellulo and in vivo, providing a promising new class of antimicrobial drug. Structures of DPAGT1 Explain Glycosylation Disease Mechanisms and Advance TB Antibiotic Design.,Dong YY, Wang H, Pike ACW, Cochrane SA, Hamedzadeh S, Wyszynski FJ, Bushell SR, Royer SF, Widdick DA, Sajid A, Boshoff HI, Park Y, Lucas R, Liu WM, Lee SS, Machida T, Minall L, Mehmood S, Belaya K, Liu WW, Chu A, Shrestha L, Mukhopadhyay SMM, Strain-Damerell C, Chalk R, Burgess-Brown NA, Bibb MJ, Barry Iii CE, Robinson CV, Beeson D, Davis BG, Carpenter EP Cell. 2018 Nov 1;175(4):1045-1058.e16. doi: 10.1016/j.cell.2018.10.037. PMID:30388443 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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