Structural basis of galactose recognition by C-type animal lectins
Structural basis of galactose recognition by C-type animal lectins
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DOI：
10.1074/jbc.271.12.6679
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发表时间：
1996-03-22
影响因子：
4.8
通讯作者：
Weis, WI
中科院分区：
文献类型：
--
作者：
Kolatkar, AR;Weis, WI
去唾液酸糖蛋白受体和许多其他C型（Ca 2+依赖性）动物凝集素特异性识别半乳糖或N-乙酰半乳糖胺封端的寡糖。类似的结合特异性可以通过改变三个氨基酸并插入富含甘氨酸的环（Iobst，S. Drickamer，K.（1994）J. Biol，Chem.269，15512-15519），与β-甲基半乳糖苷和N-乙酰半乳糖胺（GalNAc）复合的该突变体的晶体结构揭示，与野生型甘露糖结合蛋白一样，糖的3-和4-OH基团直接配位Ca 2+并与也用作Ca 2+配体的氨基酸形成氢键，甘露糖和半乳糖中3-和4-OH基团的不同立体化学，结合固定的Ca 2+配位几何形状，导致两种情况下吡喃糖环的位置不同。富含甘氨酸的环通过将关键的色氨酸保持在最适合与半乳糖的非极性面包装但与甘露糖结合不相容的位置，提供了对甘露糖的选择性。GalNAc的2-乙酰氨基取代基位于通过定点诱变鉴定的氨基酸位置附近（Iobst，S. Drickamer，K.（1996）J，Biol，Chem.271，6686-6693），因为其对于GalNAc选择性结合位点的形成是重要的。
The asialoglycoprotein receptors and many other C-type (Ca2+-dependent) animal lectins specifically recognize galactose- or N-acetylgalactosamine-terminated oligosaccharides. Analogous binding specificity can be engineered into the homologous rat mannose-binding protein A by changing three amino acids and inserting a glycine-rich loop (Iobst, S. T,, and Drickamer, K. (1994) J. Biol, Chem. 269, 15512-15519), Crystal structures of this mutant complexed with beta-methyl galactoside and N-acetylgalactosamine (GalNAc) reveal that as with wild-type mannose-binding proteins, the 3- and 4-OH groups of the sugar directly coordinate Ca2+ and form hydrogen bonds with amino acids that also serve as Ca2+ ligands, The different stereochemistry of the 3- and 4-OH groups in mannose and galactose, combined with a fixed Ca2+ coordination geometry, leads to different pyranose ring locations in the two cases. The glycine-rich loop provides selectivity against mannose by holding a critical tryptophan in a position optimal for packing with the apolar face of galactose but incompatible with mannose binding, The 2-acetamido substituent of GalNAc is in the vicinity of amino acid positions identified by site-directed mutagenesis (Iobst, S. T,, and Drickamer, K. (1996) J, Biol, Chem. 271, 6686-6693) as being important for the formation of a GalNAc-selective binding site.