Sugar-nucleotide donor specificity of histo-blood group A and B transferases is based on amino acid substitutions.
Sugar-nucleotide donor specificity of histo-blood group A and B transferases is based on amino acid substitutions.
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发表时间：
1990-11
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通讯作者：
F. Yamamoto;S. Hakomori
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作者：
F. Yamamoto;S. Hakomori
在组织血型A和B转移酶的cDNA编码区之间发现了四个氨基酸取代（aa 176、235、266和268）（Yamamoto F.，克劳森，H.，白色，T.，马尔肯，J.，和Hakomori，S.（1990）Nature 345，229-233）。在这里，我们建立了这些糖基转移酶对核苷酸糖（UDP-GalNAc或UDP-Gal）的差异亲和力的基础。在基因重建实验和DNA转染HeLa细胞中的表达研究的基础上，发现第三和第四个氨基酸取代（A中的亮氨酸和甘氨酸以及B中的甲硫氨酸和丙氨酸）在确定核苷酸-糖特异性中是至关重要的，所述氨基酸取代被计算为改变蛋白质的柔性。第二个取代（A中的甘氨酸和B中的丝氨酸）也影响特异性。我们还创造了催化GalNAc和Gal转移的新酶，并可能提供罕见的顺式AB表型的解释。
Four amino acid substitutions (aa 176, 235, 266, and 268) have been found between the coding regions of cDNAs for histo-blood group A and B transferases (Yamamoto F., Clausen, H., White, T., Marken, J., and Hakomori, S. (1990) Nature 345, 229-233). Here we establish the basis of differential affinity of these glycosyltransferases to nucleotide-sugar (UDP-GalNAc or UDP-Gal). On the basis of gene reconstruction experiments and studies of expression in DNA transfected HeLa cells, the third as well as the fourth aa substitutions (leucine and glycine in A and methionine and alanine in B), which were calculated to modify flexibility of the protein, were found to be crucial in determining nucleotide-sugar specificity. The second substitution (glycine in A and serine in B) also affects the specificity. We have also created new enzymes which catalyze the transfer of both GalNAc and Gal, and may provide an explanation of the rare cis-AB phenotype.