Computational structural analysis of an anti-L-amino acid antibody and inversion of its stereoselectivity.
Computational structural analysis of an anti-L-amino acid antibody and inversion of its stereoselectivity.
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抗 L-氨基酸抗体的计算结构分析及其立体选择性的反转。
DOI：
10.1002/jssc.200800694
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发表时间：
2009
影响因子：
3.1
通讯作者：
Hofstetter,Oliver
中科院分区：
文献类型：
--
作者：
Ranieri,DanielI;Hofstetter,Heike;Hofstetter,Oliver
使用程序SWISS-MODEL对单克隆抗-L-氨基酸抗体（抗-L-AA）的结合位点进行建模。与苯丙氨酸对映体的对接实验表明，抗体通过氢键和疏水接触与L-苯丙氨酸相互作用，而D-对映体由于空间位阻而被排斥。该抗体和抗-D-氨基酸抗体（抗-D-AA）的序列比较表明，两种免疫球蛋白均来源于相同的生殖系祖细胞。四个氨基酸残基的取代，三个在框架中，一个在互补决定区（CDR）中，允许在计算机上将抗L-AA转化为立体选择性结合D-苯丙氨酸的抗体。
The binding site of a monoclonal anti‐L‐amino acid antibody (anti‐L‐AA) was modeled using the program SWISS‐MODEL. Docking experiments with the enantiomers of phenylalanine revealed that the antibody interacts withL‐phenylalanineviahydrogen bonds and hydrophobic contacts, whereas theD‐enantiomer is rejected due to steric hindrance. Comparison of the sequences of this antibody and an anti‐D‐amino acid antibody (anti‐D‐AA) indicates that both immunoglobulins derived from the same germline progenitor. Substitution of four amino acids residues, three in the framework and one in the complementarity determining regions (CDRs), allowedin silicoconversion of the anti‐L‐AA into an antibody that stereoselectively bindsD‐phenylalanine.