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A comparison of the crystallographic structures of two catalytic antibodies with esterase activity

机译:两种具有酯酶活性的催化抗体的晶体结构比较

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The crystallographic structure of the Fab fragment of the catalytic antibody, 29G11, complexed with an (S)-norleucine phenyl phosphonate transition state analog was determined at 2.2 Angstrom resolution. The antibody catalyzes the hydrolysis of norleucine phenyl ester with(S)-enantioselectivity. The shape and charge complementarity of the binding pocket for the hapten account for the preferential binding of the (S)-enantiomer of the substrate. The structure is compared to that of the more catalytically efficient antibody, 17E8, induced by the same hapten transition state analog. 29G11 has different residues from 17E8 at eight positions in the heavy chain, including four substitutions in the hapten-binding pocket: A33V, S95G, S99R and Y100(A)N, and four substitutions at positions remote from the catalytic site, I28T, R40K, V65G and F91L. The two antibodies show large differences in the orientations of their variable and constant domains, reflected by a 32 degrees difference in their elbow angles. The V-L and V-H domains in the two antibodies differ by a rotation of 8.8 degrees. The hapten binds in similar orientations and locations in 29G11 and 17E8, which appear to have catalytic groups in common, though the changes in the association of the variable domains affect the precise positioning of residues in the hapten-binding pocket. (C) 1998 Academic Press. [References: 32]
机译:以2.2埃的分辨率测定了与(S)-正亮氨酸苯基膦酸酯过渡态类似物复合的催化抗体29G11的Fab片段的晶体结构。该抗体以(S)-对映选择性催化正亮氨酸苯基酯的水解。半抗原的结合袋的形状和电荷互补性解释了底物的(S)-对映异构体的优先结合。将该结构与由相同的半抗原过渡态类似物诱导的具有更高催化效率的抗体17E8进行了比较。 29G11在重链的八个位置与17E8具有不同的残基,包括在半抗原结合口袋中的四个取代:A33V,S95G,S99R和Y100(A)N,以及在远离催化位点的位置四个取代I28T,R40K ,V65G和F91L。两种抗体在其可变域和恒定域的方向上显示出很大的差异,这通过它们的肘角32度的差异反映出来。两种抗体中的V-L和V-H结构域相差8.8度。半抗原在29G11和17E8中以相似的方向和位置结合,它们似乎具有共同的催化基团,尽管可变域关联的变化会影响残基在半抗原结合袋中的精确定位。 (C)1998年学术出版社。 [参考:32]

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