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000168905 1001_ $$0P:(DE-HGF)0$$aPonomarenko, Natalia$$b0$$eCorresponding Author
000168905 245__ $$aRole of κ→λ light-chain constant-domain switch in the structure and functionality of A17 reactibody
000168905 260__ $$aCopenhagen$$bMunksgaard$$c2014
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000168905 520__ $$aThe engineering of catalytic function in antibodies requires precise information on their structure. Here, results are presented that show how the antibody domain structure affects its functionality. The previously designed organophosphate-metabolizing reactibody A17 has been re-engineered by replacing its constant κ light chain by the λ chain (A17λ), and the X-ray structure of A17λ has been determined at 1.95 Å resolution. It was found that compared with A17κ the active centre of A17λ is displaced, stabilized and made more rigid owing to interdomain interactions involving the CDR loops from the VL and VH domains. These VL/VH domains also have lower mobility, as deduced from the atomic displacement parameters of the crystal structure. The antibody elbow angle is decreased to 126° compared with 138° in A17κ. These structural differences account for the subtle changes in catalytic efficiency and thermodynamic parameters determined with two organophosphate ligands, as well as in the affinity for peptide substrates selected from a combinatorial cyclic peptide library, between the A17κ and A17λ variants. The data presented will be of interest and relevance to researchers dealing with the design of antibodies with tailor-made functions.
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000168905 7001_ $$0P:(DE-H253)PIP1094717$$aChatziefthymiou, Spyridon$$b1$$udesy
000168905 7001_ $$0P:(DE-H253)PIP1016968$$aKurkova, Inna$$b2
000168905 7001_ $$0P:(DE-HGF)0$$aMokrushina, Yuliana$$b3
000168905 7001_ $$0P:(DE-HGF)0$$aStepanova, Anastasiya$$b4
000168905 7001_ $$0P:(DE-HGF)0$$aSmirnov, Ivan$$b5
000168905 7001_ $$0P:(DE-HGF)0$$aAvakyan, Marat$$b6
000168905 7001_ $$0P:(DE-HGF)0$$aBobik, Tatyana$$b7
000168905 7001_ $$0P:(DE-HGF)0$$aMamedov, Azad$$b8
000168905 7001_ $$0P:(DE-HGF)0$$aMitkevich, Vladimir$$b9
000168905 7001_ $$0P:(DE-HGF)0$$aBelogurov, Alexey$$b10
000168905 7001_ $$0P:(DE-HGF)0$$aFedorova, Olga S.$$b11
000168905 7001_ $$0P:(DE-HGF)0$$aDubina, Michael$$b12
000168905 7001_ $$0P:(DE-HGF)0$$aGolovin, Andrey$$b13
000168905 7001_ $$0P:(DE-H253)PIP1002108$$aLamzin, Victor$$b14
000168905 7001_ $$0P:(DE-HGF)0$$aFriboulet, Alain$$b15
000168905 7001_ $$0P:(DE-HGF)0$$aMakarov, Alexander A.$$b16
000168905 7001_ $$0P:(DE-H253)PIP1001283$$aWilmanns, Matthias$$b17
000168905 7001_ $$0P:(DE-HGF)0$$aGabibov, Alexander$$b18
000168905 773__ $$0PERI:(DE-600)2020492-9$$a10.1107/S1399004713032446$$gVol. 70, no. 3, p. 708 - 719$$n3$$p708 - 719$$tActa crystallographica / D$$v70$$x1399-0047$$y2014
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