TY  - JOUR
AU  - Ponomarenko, Natalia
AU  - Chatziefthymiou, Spyridon
AU  - Kurkova, Inna
AU  - Mokrushina, Yuliana
AU  - Stepanova, Anastasiya
AU  - Smirnov, Ivan
AU  - Avakyan, Marat
AU  - Bobik, Tatyana
AU  - Mamedov, Azad
AU  - Mitkevich, Vladimir
AU  - Belogurov, Alexey
AU  - Fedorova, Olga S.
AU  - Dubina, Michael
AU  - Golovin, Andrey
AU  - Lamzin, Victor
AU  - Friboulet, Alain
AU  - Makarov, Alexander A.
AU  - Wilmanns, Matthias
AU  - Gabibov, Alexander
TI  - Role of κ→λ light-chain constant-domain switch in the structure and functionality of A17 reactibody
JO  - Acta crystallographica / D
VL  - 70
IS  - 3
SN  - 1399-0047
CY  - Copenhagen
PB  - Munksgaard
M1  - DESY-2014-02720
SP  - 708 - 719
PY  - 2014
AB  - 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.
LB  - PUB:(DE-HGF)16
UR  - <Go to ISI:>//WOS:000332406600010
C6  - pmid:24598740
DO  - DOI:10.1107/S1399004713032446
UR  - https://bib-pubdb1.desy.de/record/168905
ER  -