Insights into the recognition of the human glycome by microbial carbohydrate-binding modules

Insights into the recognition of the human glycome by microbial carbohydrate-binding modules
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DOI:
10.1016/j.sbi.2012.07.009
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发表时间:
2012-10-01
影响因子:
6.8
通讯作者:
Boraston, Alisdair B.
Boraston, Alisdair B.
中科院分区:
生物学2区
文献类型:
--
作者:
Ficko-Blean, Elizabeth;Boraston, Alisdair B.

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哺乳动物的多糖通常是非常复杂的,因此共生细菌和细菌病原体都开发了专门的、通常是复杂的碳水化合物活性酶(CAZyme)系统来与这些糖相互作用。这些酶往往是多模块的,具有模块化功能,最常见的是催化(糖苷水解酶催化模块)或碳水化合物结合模块(碳水化合物结合模块或CBM)。对五个CBM家族的结构-功能研究揭示了复杂哺乳动物碳水化合物的特殊性。这些CBM家族中的三个(32、47和51)在他们的β-三明治折叠之间显示出显著的结构相似性,这表明它们是共同的进化前体,但具有不同的结合特异性。家族40和41的CBM分别通过不同的糖结合模式识别唾液酸和糖原,尽管它们也采用所有的β结构折叠。完整CAZymes产生的新模型的结构视图表明,CBM部署有三种不同的模式:(I)催化位置的形成,(Ii)协同催化和结合,(Iii)一般底物附着。
Mammalian glycans are often very complex and consequently both commensal bacteria and bacterial pathogens have developed specialized and often elaborate carbohydrate-active enzyme (CAZyme) systems to interact with these sugars. These enzymes are frequently multimodular, with modular functions most often conferring catalysis (glycoside hydrolase catalytic modules) or carbohydrate-binding (carbohydrate-binding modules or CBMs). Structure-function studies of five CBM families are revealing specificities for complex mammalian carbohydrates. Three of these CBM families (32, 47, and 51) show significant structural identity between their beta-sandwich folds, suggesting a shared evolutionary precursor, but have divergent binding specificities. The family 40 and 41 CBMs recognize sialic acid and glycogen, respectively, through different modes of sugar binding, though they also adopt all beta-structure folds. A structural view of new models generated for complete CAZymes suggests three distinct modes of CBM deployment: (i) formation of the catalytic site, (ii) coordinated catalysis and binding, and (iii) general substrate adherence.