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@ARTICLE{Ponomarenko:168905,
author = {Ponomarenko, Natalia and Chatziefthymiou, Spyridon and
Kurkova, Inna and Mokrushina, Yuliana and Stepanova,
Anastasiya and Smirnov, Ivan and Avakyan, Marat and Bobik,
Tatyana and Mamedov, Azad and Mitkevich, Vladimir and
Belogurov, Alexey and Fedorova, Olga S. and Dubina, Michael
and Golovin, Andrey and Lamzin, Victor and Friboulet, Alain
and Makarov, Alexander A. and Wilmanns, Matthias and
Gabibov, Alexander},
title = {{R}ole of κ→λ light-chain constant-domain switch in the
structure and functionality of {A}17 reactibody},
journal = {Acta crystallographica / D},
volume = {70},
number = {3},
issn = {1399-0047},
address = {Copenhagen},
publisher = {Munksgaard},
reportid = {DESY-2014-02720},
pages = {708 - 719},
year = {2014},
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.},
cin = {EMBL-User / EMBL},
ddc = {570},
cid = {I:(DE-H253)EMBL-User-20120814 / I:(DE-H253)EMBL-20120731},
pnm = {PETRA Beamline P14 (POF2-54G14)},
pid = {G:(DE-H253)POF2-P14-20130405},
experiment = {EXP:(DE-H253)P-P14-20150101},
typ = {PUB:(DE-HGF)16},
UT = {WOS:000332406600010},
pubmed = {pmid:24598740},
doi = {10.1107/S1399004713032446},
url = {https://bib-pubdb1.desy.de/record/168905},
}