3ZL4

Antibody structural organization: Role of kappa - lambda chain constant domain switch in catalytic functionality

3ZL4 の概要

• エントリーDOI: 10.2210/pdb3zl4/pdb
• 分子名称: A17 ANTIBODY FAB FRAGMENT HEAVY CHAIN, A17 ANTIBODY FAB FRAGMENT LAMBDA LIGHT CHAIN, 2-(N-MORPHOLINO)-ETHANESULFONIC ACID, ... (4 entities in total)
• 機能のキーワード: immune system
• 由来する生物種: Homo sapiens (HUMAN); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 53726.28

構造登録者

Chatziefthimiou, S.D.,Ponomarenko, N.A.,Kurkova, I.N.,Smirnov, A.V.,Smirnov, I.V.,Lamzin, V.S.,Gabibov, A.G.,Wilmanns, M. (登録日: 2013-01-28, 公開日: 2014-02-05, 最終更新日: 2024-11-13)

主引用文献

Ponomarenko, N.A.,Chatziefthimiou, S.D.,Kurkova, I.N.,Mokrushina, Y.A.,Stepanova, A.V.,Smirnov, I.V.,Avakyan, E.M.,Bobik, T.V.,Mamedov, A.,Mitkevich, V.A.,Belogurov, A.J.,Fedorova, O.S.,Dubina, M.,Golovin, A.,Lamzin, V.S.,Friboulet, A.,Makarov, A.A.,Wilmanns, M.,Gabibov, A.G.
Role of Kappa>Lambda Light-Chain Constant-Domain Switch in the Structure and Functionality of A17 Reactibody
Acta Crystallogr.,Sect.D, 70:708-, 2014

PubMed Abstract: The engineering of catalytic function in antibodies requires precise information on their structure. Here, results are presented that show how the antibody domain structure affects its functionality. The previously designed organophosphate-metabolizing reactibody A17 has been re-engineered by replacing its constant κ light chain by the λ chain (A17λ), and the X-ray structure of A17λ has been determined at 1.95 Å resolution. It was found that compared with A17κ the active centre of A17λ is displaced, stabilized and made more rigid owing to interdomain interactions involving the CDR loops from the VL and VH domains. These VL/VH domains also have lower mobility, as deduced from the atomic displacement parameters of the crystal structure. The antibody elbow angle is decreased to 126° compared with 138° in A17κ. These structural differences account for the subtle changes in catalytic efficiency and thermodynamic parameters determined with two organophosphate ligands, as well as in the affinity for peptide substrates selected from a combinatorial cyclic peptide library, between the A17κ and A17λ variants. The data presented will be of interest and relevance to researchers dealing with the design of antibodies with tailor-made functions.

PubMed: 24598740
DOI: 10.1107/S1399004713032446

実験手法

X-RAY DIFFRACTION (1.95 Å)