Structures of the antibody 64M-5 Fab and its complex with dT(6 – 4)T indicate induced-fit and high-affinity mechanisms

DNA photoproducts with (6 – 4) pyrimidine – pyrimidone adducts produced by ultraviolet light are mutagenic and carcinogenic. The crystal structures of the anti-(6 – 4) photoproduct antibody 64M-5 Fab and of its complex with dT(6 – 4)T were determined at 2.5 and 2.0   Å resolution, respectively. A comparison between the dT(6 – 4)T-liganded and unliganded structures indicates that the side chain of His93L is greatly rotated and shifted on binding to dT(6 – 4)T, leading to the formation of an electrostatic interaction with the phosphate moiety of dT(6 – 4)T, which shows a remarkable induced fit. Based on a comparison of the dT(6 – 4)T-liganded structures of the 64M-5 and 64M-2 Fabs, the electrostatic interaction between the side chain of His93L in 64M-5 and the phosphate moiety of dT(6 – 4)T is lost for Leu93L in 64M-2, while Arg90L in 64M-5 instead of Gln90L in 64M-2 stabilizes the conformation of complementarity-determining region (CDR) L3. These differences contribute to the higher affinity of 64M-5 for dT(6 – 4)T compared with that of 64M-2.
Source: Acta Crystallographica Section F - Category: Biochemistry Authors: Tags: antibodies Fabs crystal structure DNA (6 – 4) photoproduct ultraviolet light research communications Source Type: research