2RI9

Penicillium citrinum alpha-1,2-mannosidase in complex with a substrate analog

2RI9 の概要

• エントリーDOI: 10.2210/pdb2ri9/pdb
• 関連するPDBエントリー: 1kkt 1kre 1krf 2RI8
• 分子名称: Mannosyl-oligosaccharide alpha-1,2-mannosidase, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]alpha-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-alpha-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (8 entities in total)
• 機能のキーワード: alternative conformations, modulation of activity, glycoprotein, glycosidase, hydrolase, secreted
• 由来する生物種: Penicillium citrinum
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 110052.45

構造登録者

Lobsanov, Y.D.,Yoshida, T.,Desmet, T.,Nerinckx, W.,Yip, P.,Claeyssens, M.,Herscovics, A.,Howell, P.L. (登録日: 2007-10-10, 公開日: 2008-03-25, 最終更新日: 2024-11-13)

主引用文献

Lobsanov, Y.D.,Yoshida, T.,Desmet, T.,Nerinckx, W.,Yip, P.,Claeyssens, M.,Herscovics, A.,Howell, P.L.
Modulation of activity by Arg407: structure of a fungal alpha-1,2-mannosidase in complex with a substrate analogue.
Acta Crystallogr.,Sect.D, 64:227-236, 2008

PubMed Abstract: Class I alpha-mannosidases (glycoside hydrolase family GH47) play key roles in the maturation of N-glycans and the ER-associated degradation of unfolded glycoproteins. The 1.95 A resolution structure of a fungal alpha-1,2-mannosidase in complex with the substrate analogue methyl-alpha-D-lyxopyranosyl-(1',2)-alpha-D-mannopyranoside (LM) shows the intact disaccharide spanning the -1/+1 subsites, with the D-lyxoside ring in the -1 subsite in the 1C4 chair conformation, and provides insight into the mechanism of catalysis. The absence of the C5' hydroxymethyl group on the D-lyxoside moiety results in the side chain of Arg407 adopting two alternative conformations: the minor one interacting with Asp375 and the major one interacting with both the D-lyxoside and the catalytic base Glu409, thus disrupting its function. Chemical modification of Asp375 has previously been shown to inactivate the enzyme. Taken together, the data suggest that Arg407, which belongs to the conserved sequence motif RPExxE, may act to modulate the activity of the enzyme. The proposed mechanism for modulating the activity is potentially a general mechanism for this superfamily.

PubMed: 18323617
DOI: 10.1107/S0907444907065572

実験手法

X-RAY DIFFRACTION (1.95 Å)