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Protein Catenation Enhances Both the Stability and Activity of Folded Structural Domains
Author(s) -
Wang XiaoWei,
Zhang WenBin
Publication year - 2017
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201705194
Subject(s) - catenation , catenane , dihydrofolate reductase , chemistry , concatenation (mathematics) , fluorescence , green fluorescent protein , combinatorial chemistry , topology (electrical circuits) , biophysics , stereochemistry , biochemistry , dna , biology , molecule , enzyme , gene , physics , mathematics , organic chemistry , combinatorics , quantum mechanics
Catenanes are intriguing molecular architectures with unique properties. Herein, we report the cellular synthesis of protein catenanes containing folded structural domains, aided by synergy between p53 dimerization and SpyTag/SpyCatcher chemistry. Concatenation of green fluorescent protein (GFP) was shown to increase chemical stability without disrupting the fluorescence properties, and concatenated dihydrofolate reductase (DHFR) exhibited a melting temperature around 4 °C higher and catalytic activity around 27 % higher than the wild‐type DHFR and the cyclic/linear controls. Catenation also confers considerable proteolytic resistance on DHFR. The results suggest that catenation could enhance both the stability and activity of folded proteins, thus making topology engineering an attractive approach for tailoring protein properties without varying their native sequences.