3zoa
The structure of Trehalose Synthase (TreS) of Mycobacterium smegmatis in complex with acarboseThe structure of Trehalose Synthase (TreS) of Mycobacterium smegmatis in complex with acarbose
Structural highlights
FunctionTRES_MYCS2 Catalyzes the reversible interconversion of maltose and trehalose by transglucosylation. Maltose is the preferred substrate. To a lesser extent, also displays amylase activity, catalyzing the endohydrolysis of (1->4)-alpha-D-glucosidic linkages in glycogen and maltooligosaccharides such as maltoheptaose, to produce maltose which then can be converted to trehalose. TreS plays a key role in the utilization of trehalose for the production of glycogen, and might also function as a sensor and/or regulator of trehalose levels within the cell. Thus, when trehalose levels in the cell become dangerously low, TreS can expedite the conversion of glycogen to maltose via its amylase activity and then convert the maltose to trehalose; but this enzyme also can expedite or promote the conversion of trehalose to glycogen when cytoplasmic trehalose levels become too high. Is also able to catalyze the hydrolytic cleavage of alpha-aryl glucosides, as well as alpha-glucosyl fluoride in vitro.[1] [2] [3] [4] Publication Abstract from PubMedTrehalose 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. The structure of the Mycobacterium smegmatis trehalose synthase reveals an unusual active site configuration and acarbose-binding mode.,Caner S, Nguyen N, Aguda A, Zhang R, Pan YT, Withers SG, Brayer GD Glycobiology. 2013 Jul 5. PMID:23735230[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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