Crystal structures of the maltodextrin/maltose-binding protein complexed with reduced oligosaccharides: Flexibility of tertiary structure and ligand binding
Crystal structures of the maltodextrin/maltose-binding protein complexed with reduced oligosaccharides: Flexibility of tertiary structure and ligand binding
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DOI：
10.1006/jmbi.2001.4456
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发表时间：
2001-03-09
影响因子：
5.6
通讯作者：
Quiocho, FA
中科院分区：
文献类型：
--
作者：
Duan, XQ;Hall, JA;Quiocho, FA
麦芽糖糊精或麦芽糖结合蛋白（细菌ABC型主动转运和趋化性的初始受体）的结构由两个球形结构域组成，所述两个球形结构域由凹槽分开，其中配体通过结构域间旋转结合和封闭。在这里，我们报告的晶体结构的蛋白质复合减少麦芽低聚糖（麦芽三糖醇和麦芽四糖醇）的“封闭”和“开放”的形式的测定。尽管这些修饰的糖与受体结合，但它们不被野生型转运蛋白转运。在封闭结构中，还原糖被埋在凹槽中并被两个结构域结合，一个结构域主要通过氢键相互作用，另一个结构域主要通过与芳族侧链的非极性相互作用。在开放的结构中，由于两个结构域之间的大分离而废除了主动运输和趋化性的细胞活性，糖几乎完全结合到富含芳香族残基的结构域。开链葡萄糖醇残基的结合位点延伸至亚位点，该亚位点不同于在活性线性麦芽低聚糖结合的先前结构研究中发现的葡萄糖残基的亚位点。该亚位点的占据也可以解释还原寡糖不能被转运的原因。这里报道的结构，结合先前确定的几个其他复合物与活性寡糖在封闭的形式，并与环糊精在开放的形式，揭示了至少四种不同的模式的配体结合，但只有一个是功能活性。这种多功能性反映了蛋白质的灵活性，从结构域间旋转的非常大的运动到更局部化的侧链构象变化，以及寡糖的适应性。(C)北京：科学出版社.
The structure of the maltodextrin or maltose-binding protein, an initial receptor for bacterial ABC-type active transport and chemotaxis, consists of two globular domains that are separated by a groove wherein the ligand is bound and enclosed by an inter-domain rotation. Here, we report the determination of the crystal structures of the protein complexed with reduced maltooligosaccharides (maltotriitol and maltotetraitol) in both the "closed" and "open" forms. Although these modified sugars bind to the receptor, they are not transported by the wild-type transporter. In the closed structures, the reduced sugars are buried in the groove and bound by both domains, one domain mainly by hydrogen-bonding interactions and the other domain primarily by non-polar interactions with aromatic side-chains. In the open structures, which abrogate both cellular activities of active transport and chemotaxis because of the large separation between the two domains, the sugars are bound almost exclusively to the domain rich in aromatic residues. The binding site for the open chain glucitol residue extends to a subsite that is distinct from those for the glucose residues that were uncovered in prior structural studies of the binding of active linear maltooligosaccharides. Occupation of this subsite may also account for the inability of the reduced oligosaccharides to be transported. The structures reported here, combined with those previously determined for several other complexes with active oligosaccharides in the closed form and with cyclodextrin in the open form, revealed at least four distinct modes of ligand binding but with only one being functionally active. This versatility reflects the flexibility of the protein, from very large motions of interdomain rotation to more localized side-chain conformational changes, and adaptation by the oligosaccharides as well. (C) 2001 Academic Press.