3ZOA

The structure of Trehalose Synthase (TreS) of Mycobacterium smegmatis in complex with acarbose

Summary for 3ZOA

• Entry DOI: 10.2210/pdb3zoa/pdb
• Related: 3ZO9
• Related PRD ID: PRD_900007
• Descriptor: TREHALOSE SYNTHASE/AMYLASE TRES, 4,6-dideoxy-4-{[(1S,4R,5S,6S)-4,5,6-trihydroxy-3-(hydroxymethyl)cyclohex-2-en-1-yl]amino}-alpha-D-glucopyranose-(1-4)-alpha-D-glucopyranose-(1-4)-alpha-D-glucopyranose, CALCIUM ION, ... (6 entities in total)
• Functional Keywords: hydrolase, glycohydrolase, drug design, tuberculosis
• Biological source: MYCOBACTERIUM SMEGMATIS
• Total number of polymer chains: 2
• Total formula weight: 137566.81

Authors

Caner, S.,Nguyen, N.,Aguda, A.,Zhang, R.,Pan, Y.T.,Withers, S.G.,Brayer, G.D. (deposition date: 2013-02-21, release date: 2013-07-17, Last modification date: 2023-12-20)

Primary citation

Caner, S.,Nguyen, N.,Aguda, A.,Zhang, R.,Pan, Y.T.,Withers, S.G.,Brayer, G.D.
The Structure of the Mycobacterium Smegmatis Trehalose Synthase Reveals an Unusual Active Site Configuration and Acarbose-Binding Mode.
Glycobiology, 23:1075-, 2013

PubMed Abstract: Trehalose synthase (TreS) catalyzes the reversible conversion of maltose into trehalose in mycobacteria as one of three biosynthetic pathways to this nonreducing disaccharide. Given the importance of trehalose to survival of mycobacteria, there has been considerable interest in understanding the enzymes involved in its production; indeed the structures of the key enzymes in the other two pathways have already been determined. Herein, we present the first structure of TreS from Mycobacterium smegmatis, thereby providing insights into the catalytic machinery involved in this intriguing intramolecular reaction. This structure, which is of interest both mechanistically and as a potential pharmaceutical target, reveals a narrow and enclosed active site pocket within which intramolecular substrate rearrangements can occur. We also present the structure of a complex of TreS with acarbose, revealing a hitherto unsuspected oligosaccharide-binding site within the C-terminal domain. This may well provide an anchor point for the association of TreS with glycogen, thereby enhancing its role in glycogen biosynthesis and degradation.

PubMed: 23735230
DOI: 10.1093/GLYCOB/CWT044

Experimental method

X-RAY DIFFRACTION (1.85 Å)