3QCT

Crystal structure of the humanized apo LT3015 anti-lysophosphatidic acid antibody Fab fragment

3QCT の概要

• エントリーDOI: 10.2210/pdb3qct/pdb
• 関連するPDBエントリー: 3QCU 3QCV
• 分子名称: LT3015 antibody Fab fragment, heavy chain, LT3015 antibody Fab fragment, light chain, SULFATE ION, ... (5 entities in total)
• 機能のキーワード: antibody, lysophosphatidic acid binding, immune system
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Secreted : P01834
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 48220.76

構造登録者

Fleming, J.K.,Wojciak, J.M.,Campbell, M.-A.,Huxford, T. (登録日: 2011-01-17, 公開日: 2011-03-30, 最終更新日: 2024-11-27)

主引用文献

Fleming, J.K.,Wojciak, J.M.,Campbell, M.A.,Huxford, T.
Biochemical and structural characterization of lysophosphatidic Acid binding by a humanized monoclonal antibody.
J.Mol.Biol., 408:462-476, 2011

PubMed Abstract: Lysophosphatidic acid (LPA) is a common product of glycerophospholipid metabolism and an important mediator of signal transduction. Aberrantly high LPA concentrations accompany multiple disease states. One potential approach for treatment of these diseases, therefore, is the therapeutic application of antibodies that recognize and bind LPA as their antigen. We have determined the X-ray crystal structure of an anti-LPA antibody (LT3015) Fab fragment in its antigen-free form to 2.15 Å resolution and in complex with two LPA isotypes (14:0 and 18:2) to resolutions of 1.98 and 2.51 Å, respectively. The variable CDR (complementarity-determining region) loops at the antigen binding site adopt nearly identical conformations in the free and antigen-bound crystal structures. The crystallographic models reveal that the LT3015 antibody employs both heavy- and light-chain CDR loops to create a network of eight hydrogen bonds with the glycerophosphate head group of its LPA antigen. The head group is almost completely excluded from contact with solvent, while the hydrocarbon tail is partially solvent-exposed. In general, mutation of amino acid residues at the antigen binding site disrupts LPA binding. However, the introduction of particular mutations chosen strategically on the basis of the structures can positively influence LPA binding affinity. Finally, these structures elucidate the exquisite specificity demonstrated by an anti-lipid antibody for binding a structurally simple and seemingly unconstrained target molecule.

PubMed: 21392506
DOI: 10.1016/j.jmb.2011.02.061

実験手法

X-RAY DIFFRACTION (2.1493 Å)