3V0N

Crystal structure of the Fucosylgalactoside alpha N-acetylgalactosaminyltransferase (GTA, cisAB mutant L266G, G268A) in complex with a novel UDP-GalNAc derived inhibitor (3GW and 4GW)

3V0N の概要

• エントリーDOI: 10.2210/pdb3v0n/pdb
• 関連するPDBエントリー: 3IOH 3IOI 3IOJ
• 分子名称: Histo-blood group ABO system transferase, MANGANESE (II) ION, 5-(5-formylthiophen-2-yl)uridine 5'-(trihydrogen diphosphate), ... (7 entities in total)
• 機能のキーワード: gta, 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
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Golgi apparatus, Golgi stack membrane; Single-pass type II membrane protein: P16442
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 71636.35

構造登録者

Palcic, M.M.,Jorgensen, R. (登録日: 2011-12-08, 公開日: 2013-01-23, 最終更新日: 2023-09-13)

主引用文献

Jrgensen, 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

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

実験手法

X-RAY DIFFRACTION (1.75 Å)