Role of κ→λ light-chain constant-domain switch in the structure and functionality of A17 reactibodyстатья

Статья опубликована в высокорейтинговом журнале

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Дата последнего поиска статьи во внешних источниках: 31 октября 2014 г.

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[1] Role of κ→λ light-chain constant-domain switch in the structure and functionality of a17 reactibody / N. Ponomarenko, S. D. Chatziefthimiou, I. Kurkova et al. // Acta Crystallographica Section D: Biological Crystallography. — 2014. — Vol. 70, no. 3. — P. 708–719. 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 [kappa] light chain by the [lambda] chain (A17[lambda]), and the X-ray structure of A17[lambda] has been determined at 1.95 Å resolution. It was found that compared with A17[kappa] the active centre of A17[lambda] 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 126o compared with 138o in A17[kappa]. 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 A17[kappa] and A17[lambda] variants. The data presented will be of interest and relevance to researchers dealing with the design of antibodies with tailor-made functions. [ DOI ]

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