Crystal structures of the maltodextrin/maltose-binding protein complexed with reduced oligosaccharides: Flexibility of tertiary structure and ligand binding

The structure of the maltodextrin or maltose-binding protein, an initial re ceptor for bacterial ABC-type active transport and chemotaxis, consists of two globular domains that are separated by a groove wherein the ligand is b ound and enclosed by an inter-domain rotation. Here, we report the determin ation of the crystal structures of the protein complexed with reduced malto oligosaccharides (maltotriitol and maltotetraitol) in both the "closed" and "open" forms. Although these modified sugars bind to the receptor, they ar e not transported by the wild-type transporter. In the closed structures, t he reduced sugars are buried in the groove and bound by both domains, one d omain mainly by hydrogen-bonding interactions and the other domain primaril y by non-polar interactions with aromatic side-chains. In the open structur es, which abrogate both cellular activities of active transport and chemota xis because of the large separation between the two domains, the sugars are bound almost exclusively to the domain rich in aromatic residues. The bind ing site for the open chain glucitol residue extends to a subsite that is d istinct from those for the glucose residues that were uncovered in prior st ructural studies of the binding of active linear maltooligosaccharides. Occ upation of this subsite may also account for the inability of the reduced o ligosaccharides to be transported. The structures reported here, combined w ith those previously determined for several other complexes with active oli gosaccharides in the closed form and with cyclodextrin in the open form, re vealed at least four distinct modes of ligand binding but with only one bei ng functionally active. This versatility reflects the flexibility of the pr otein, from very large motions of interdomain rotation to more localized si de-chain conformational changes, and adaptation by the oligosaccharides as well. (C) 2001 Academic Press.