Department of Tumor Development, Burnham Institute for Medical Research, La Jolla, California, USA.
Transfusion. 2010 Mar;50(3):622-30. doi: 10.1111/j.1537-2995.2009.02463.x. Epub 2009 Nov 20.
The alpha1,3-galactosyl epitope (alpha1-3Gal epitope), a major xenotransplant antigen, is synthesized by alpha1,3-galactosyltransferase (alpha1-3Gal transferase), which is evolutionarily related to the histo-blood group A/B transferases.
We constructed structural chimeras between the human type A and murine alpha1-3Gal transferases and examined their activity and specificity.
In many instances, a total loss of transferase activity was observed. Certain areas could be exchanged, with a potential diminishing of activity. With a few constructs, changes in acceptor substrate specificity were suspected. Unexpectedly, a functional conversion from A to B transferase activity was observed after replacing the short sequence of human A transferase with the corresponding sequence from murine alpha1-3Gal transferase.
Because these two paralogous enzymes differ in 16 positions of the 38 amino acid residues in the replaced region, our finding may suggest that despite separate evolution and diversified acceptors, these glycosyltransferases still share the three-dimensional domain structure that is responsible for their sugar specificity, arguing against the functional requirement of a strong purifying selection playing a role in the evolution of the ABO family of genes.
α1,3-半乳糖苷表位（α1-3Gal 表位）是一种主要的异种移植抗原，由α1,3-半乳糖基转移酶（α1-3Gal 转移酶）合成，该酶在进化上与组织血型 A/B 转移酶有关。
我们构建了人 A 型和鼠 α1,3Gal 转移酶之间的结构嵌合体，并研究了它们的活性和特异性。
在许多情况下，观察到转移酶活性完全丧失。某些区域可以交换，活性可能会降低。对于一些构建体，怀疑接受体底物特异性发生了变化。出乎意料的是，在用来自鼠 α1,3Gal 转移酶的相应序列替换人 A 转移酶的短序列后，观察到从 A 转移酶到 B 转移酶活性的功能性转换。
由于这两种平行酶在替换区域的 38 个氨基酸残基中有 16 个位置不同，我们的发现可能表明，尽管这两种酶在进化上是独立的，且接受体多样化，但它们仍然共享负责其糖特异性的三维结构域结构，这表明在 ABO 基因家族的进化中，强烈的净化选择并不起作用。
