Crystal Structure of Thermotoga maritima α-Glucosidase AglA Defines a New Clan of NAD+-dependent Glycosidases

Lodge, Jacinta A. and Maier, Timm and Liebl, Wolfgang and Hoffmann, Volker and Sträter, Norbert. (2003) Crystal Structure of Thermotoga maritima α-Glucosidase AglA Defines a New Clan of NAD+-dependent Glycosidases. Journal of Biological Chemistry, 278 (21). pp. 19151-19158.

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Glycoside hydrolase family 4 represents an unusual group of glucosidases with a requirement for NAD(+), divalent metal cations, and reducing conditions. The family is also unique in its inclusion of both alpha- and beta-specific enzymes. The alpha-glucosidase A, AglA, from Thermotoga maritima is a typical glycoside hydrolase family 4 enzyme, requiring NAD(+) and Mn2+ as well as strongly reducing conditions for activity. Here we present the crystal structure of the protein complexed with NAD(+) and maltose, refined at a resolution of 1.9 Angstrom. The NAD(+) is bound to a typical Rossman fold NAD(+)-binding site, and the nicotinamide moiety is localized close to the maltose substrate. Within the active site the conserved Cys-174 and surrounding histidines are positioned to play a role in the hydrolysis reaction. The electron density maps indicate that Cys-174 is oxidized to a sulfinic acid. Most likely, the strongly reducing conditions are necessary to reduce the oxidized cysteine side chain. Notably, the canonical set of catalytic acidic residues common to other glucosidases is not present in the active site. This, combined with a high structural homology to NAD-dependent dehydrogenases, suggests an unusual and possibly unique mechanism of action for a glycoside-hydrolyzing enzyme.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Structural Biology & Biophysics > Structural Biology (Maier)
UniBasel Contributors:Maier, Timm
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:American Society for Biochemistry and Molecular Biology
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:14 Oct 2016 10:26
Deposited On:14 Oct 2016 10:26

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