1B41

HUMAN ACETYLCHOLINESTERASE COMPLEXED WITH FASCICULIN-II, GLYCOSYLATED PROTEIN

1B41 の概要

• エントリーDOI: 10.2210/pdb1b41/pdb
• 分子名称: ACETYLCHOLINESTERASE, FASCICULIN-2, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
• 機能のキーワード: serine esterase, human-acetylcholinesterase, hydrolase, snake toxin, hydrolase-toxin complex, hydrolase/toxin
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 66664.26

構造登録者

Kryger, G.,Harel, M.,Shafferman, A.,Silman, I.,Sussman, J.L. (登録日: 1999-01-05, 公開日: 2001-01-17, 最終更新日: 2024-11-13)

主引用文献

Kryger, G.,Harel, M.,Giles, K.,Toker, L.,Velan, B.,Lazar, A.,Kronman, C.,Barak, D.,Ariel, N.,Shafferman, A.,Silman, I.,Sussman, J.L.
Structures of recombinant native and E202Q mutant human acetylcholinesterase complexed with the snake-venom toxin fasciculin-II.
Acta Crystallogr.,Sect.D, 56:1385-1394, 2000

PubMed Abstract: Structures of recombinant wild-type human acetylcholinesterase and of its E202Q mutant as complexes with fasciculin-II, a 'three-finger' polypeptide toxin purified from the venom of the eastern green mamba (Dendroaspis angusticeps), are reported. The structure of the complex of the wild-type enzyme was solved to 2.8 A resolution by molecular replacement starting from the structure of the complex of Torpedo californica acetylcholinesterase with fasciculin-II and verified by starting from a similar complex with mouse acetylcholinesterase. The overall structure is surprisingly similar to that of the T. californica enzyme with fasciculin-II and, as expected, to that of the mouse acetylcholinesterase complex. The structure of the E202Q mutant complex was refined starting from the corresponding wild-type human acetylcholinesterase structure, using the 2.7 A resolution data set collected. Comparison of the two structures shows that removal of the charged group from the protein core and its substitution by a neutral isosteric moiety does not disrupt the functional architecture of the active centre. One of the elements of this architecture is thought to be a hydrogen-bond network including residues Glu202, Glu450, Tyr133 and two bridging molecules of water, which is conserved in other vertebrate acetylcholinesterases as well as in the human enzyme. The present findings are consistent with the notion that the main role of this network is the proper positioning of the Glu202 carboxylate relative to the catalytic triad, thus defining its functional role in the interaction of acetylcholinesterase with substrates and inhibitors.

PubMed: 11053835
DOI: 10.1107/S0907444900010659

実験手法

X-RAY DIFFRACTION (2.76 Å)