Zitieren Sie bitte immer diesen URN: urn:nbn:de:kobv:b43-358987
Fluorine teams up with water to restore inhibitor activity to mutant BPTI
- Introducing fluorine into molecules has a wide range of effects on their physicochemical properties, often desirable but in most cases unpredictable. The fluorine atom imparts the C–F bond with low polarizability and high polarity, and significantly affects the behavior of neighboring functional groups, in a covalent or noncovalent manner. Here, we report that fluorine, present in the form of a single fluoroalkyl amino acid side chain in the P1 position of the well-characterized serine-protease inhibitor BPTI, can fully restore inhibitor activity to a mutant that contains the corresponding hydrocarbon side chain at the same site. High resolution crystal structures were obtained for four BPTI variants in complex with bovine b-trypsin, revealing changes in the stoichiometry and dynamics of water molecules in the S1 subsite. These results demonstrate that the introduction of fluorine into a protein environment can result in “chemical complementation” that has a significantly favorableIntroducing fluorine into molecules has a wide range of effects on their physicochemical properties, often desirable but in most cases unpredictable. The fluorine atom imparts the C–F bond with low polarizability and high polarity, and significantly affects the behavior of neighboring functional groups, in a covalent or noncovalent manner. Here, we report that fluorine, present in the form of a single fluoroalkyl amino acid side chain in the P1 position of the well-characterized serine-protease inhibitor BPTI, can fully restore inhibitor activity to a mutant that contains the corresponding hydrocarbon side chain at the same site. High resolution crystal structures were obtained for four BPTI variants in complex with bovine b-trypsin, revealing changes in the stoichiometry and dynamics of water molecules in the S1 subsite. These results demonstrate that the introduction of fluorine into a protein environment can result in “chemical complementation” that has a significantly favorable impact on protein–protein interactions.…
Autor*innen: | S. Ye, B. Loll, A. Berger, Ulrike Mülow, C. Alings, M. Wahl, B. Koksch |
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Dokumenttyp: | Zeitschriftenartikel |
Veröffentlichungsform: | Verlagsliteratur |
Sprache: | Englisch |
Titel des übergeordneten Werkes (Englisch): | Chemical Science |
Jahr der Erstveröffentlichung: | 2015 |
Veröffentlichende Institution: | Bundesanstalt für Materialforschung und -prüfung (BAM) |
Verlag: | Royal Society of Chemistry |
Verlagsort: | Cambridge |
Ausgabe/Heft: | 9 |
Erste Seite: | 5246 |
Letzte Seite: | 5254 |
DDC-Klassifikation: | Naturwissenschaften und Mathematik / Chemie / Analytische Chemie |
Freie Schlagwörter: | Peptide synthesis; crystal structures; serine-protease inhibitor |
DOI: | 10.1039/C4SC03227F |
URN: | urn:nbn:de:kobv:b43-358987 |
Verfügbarkeit des Dokuments: | Datei für die Öffentlichkeit verfügbar ("Open Access") |
Lizenz (Deutsch): | Creative Commons - Namensnennung-Nicht kommerziell |
Datum der Freischaltung: | 29.04.2016 |
Referierte Publikation: | Nein |
Schriftenreihen ohne Nummerierung: | Wissenschaftliche Artikel der BAM |