6IDG

antibody 64M-5 Fab in complex with dT(6-4)T

Summary for 6IDG

• Entry DOI: 10.2210/pdb6idg/pdb
• Descriptor: Anti-(6-4) photoproduct antibody 64M-5 Fab (light chain), Anti-(6-4) photoproduct antibody 64M-5 Fab (heavy chain), DNA (5'-D(*(64T)P*(5PY))-3'), ... (4 entities in total)
• Functional Keywords: dna (6-4) photoproduct, immunoglobulin, fab, immune system
• Biological source: Mus musculus; More
• Total number of polymer chains: 3
• Total formula weight: 48387.66

Authors

Yokoyama, H.,Mizutani, R.,Noguchi, S.,Hayashida, N. (deposition date: 2018-09-10, release date: 2019-02-13, Last modification date: 2024-10-09)

Primary citation

Yokoyama, H.,Mizutani, R.,Noguchi, S.,Hayashida, N.
Structures of the antibody 64M-5 Fab and its complex with dT(6-4)T indicate induced-fit and high-affinity mechanisms.
Acta Crystallogr.,Sect.F, 75:80-88, 2019

PubMed Abstract: 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.

PubMed: 30713158
DOI: 10.1107/S2053230X18017661

Experimental method

X-RAY DIFFRACTION (2 Å)