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3V0O

Crystal structure of the Fucosylgalactoside alpha N-acetylgalactosaminyltransferase (GTA, cisAB mutant L266G, G268A) in complex with a novel UDP-GalNAc derived inhibitor (4GW) and H-antigen acceptor

Summary for 3V0O
Entry DOI10.2210/pdb3v0o/pdb
Related3IOH 3IOI 3IOJ
DescriptorHisto-blood group ABO system transferase, MANGANESE (II) ION, 5-(5-formylthiophen-2-yl)uridine 5'-(trihydrogen diphosphate), ... (6 entities in total)
Functional Keywordsgta, abo, cisab mutant, rossmann fold, "closed" conformation, glycosyltransferase, glycoprotein, blood group antigen, udp-galnac, metal-binding, manganese, glycosylation, transmembrane, golgi apparatus, secreted, signal-anchor, transferase-transferase inhibitor complex, transferase/transferase inhibitor
Biological sourceHomo sapiens (human)
Cellular locationGolgi apparatus, Golgi stack membrane; Single-pass type II membrane protein: P16442
Total number of polymer chains2
Total formula weight71419.57
Authors
Palcic, M.M.,Jorgensen, R. (deposition date: 2011-12-08, release date: 2013-01-23, Last modification date: 2023-09-13)
Primary citationJrgensen, R.,Pesnot, T.,Lee, H.J.,Palcic, M.M.,Wagner, G.K.
Base-modified donor analogues reveal novel dynamic features of a glycosyltransferase.
J.Biol.Chem., 288:26201-26208, 2013
Cited by
PubMed Abstract: Glycosyltransferases (GTs) are enzymes that are involved, as Nature's "glycosylation reagents," in many fundamental biological processes including cell adhesion and blood group biosynthesis. Although of similar importance to that of other large enzyme families such as protein kinases and proteases, the undisputed potential of GTs for chemical biology and drug discovery has remained largely unrealized to date. This is due, at least in part, to a relative lack of GT inhibitors and tool compounds for structural, mechanistic, and cellular studies. In this study, we have used a novel class of GT donor analogues to obtain new structural and enzymological information for a representative blood group GT. These analogues interfere with the folding of an internal loop and the C terminus, which are essential for catalysis. Our experiments have led to the discovery of an entirely new active site folding mode for this enzyme family, which can be targeted in inhibitor development, similar to the DFG motif in protein kinases. Taken together, our results provide new insights into substrate binding, dynamics, and utilization in this important enzyme family, which can very likely be harnessed for the rational development of new GT inhibitors and probes.
PubMed: 23836908
DOI: 10.1074/jbc.M113.465963
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (1.65 Å)
Structure validation

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