In Situ Cyclization of Native Proteins: Structure‐Based Design of a Bicyclic Enzyme
Abstract: Increased tolerance of enzymes towards thermal and chemical stress is required for many applications and can be achieved by macrocyclization of the enzyme resulting in the stabilizing of its tertiary structure. Thus far, macrocyclization approaches utilize a very limited structural diversity, which complicates the design process. Herein, we report an approach that enables cyclization through the installation of modular crosslinks into native proteins composed entirely of proteinogenic amino acids. Our stabilization procedure involves the introduction of three surface‐exposed cysteine residues, which are reacted with a triselectrophile, resulting in the in situ cyclization of the protein (INCYPRO). A bicyclic version of sortase A was designed that exhibits increased tolerance towards thermal as well as chemical denaturation, and proved to be efficient in protein labeling under denaturing conditions. In addition, we applied INCYPRO to the KIX domain, resulting in up to 24 °C increased thermal stability.
- Standort
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Deutsche Nationalbibliothek Frankfurt am Main
- Umfang
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Online-Ressource
- Sprache
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Englisch
- Erschienen in
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In Situ Cyclization of Native Proteins: Structure‐Based Design of a Bicyclic Enzyme ; volume:57 ; number:35 ; year:2018 ; pages:11164-11170 ; extent:7
Angewandte Chemie / International edition. International edition ; 57, Heft 35 (2018), 11164-11170 (gesamt 7)
- Urheber
- DOI
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10.1002/anie.201804506
- URN
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urn:nbn:de:101:1-2022090508241981521878
- Rechteinformation
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Letzte Aktualisierung
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15.08.2025, 07:37 MESZ
Datenpartner
Deutsche Nationalbibliothek. Bei Fragen zum Objekt wenden Sie sich bitte an den Datenpartner.
Beteiligte
- Pelay‐Gimeno, Marta
- Bange, Tanja
- Hennig, Sven
- Großmann, Tom N.
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