dc.contributor.author
Ye, Shijie
dc.contributor.author
Loll, Bernhard
dc.contributor.author
Berger, Allison Ann
dc.contributor.author
Mülow, Ulrike
dc.contributor.author
Alings, Claudia
dc.contributor.author
Wahl, Markus C.
dc.contributor.author
Koksch, Beate
dc.date.accessioned
2018-06-08T03:22:16Z
dc.date.available
2015-12-10T08:52:12.129Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/15032
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-19220
dc.description.abstract
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 β-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.
en
dc.rights.uri
http://creativecommons.org/licenses/by-nc/3.0/
dc.subject.ddc
500 Naturwissenschaften und Mathematik::540 Chemie
dc.title
Fluorine teams up with water to restore inhibitor activity to mutant BPTI
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation
Chemical Science. - 6 (2015), 9, S. 5246-5254
dcterms.bibliographicCitation.doi
10.1039/C4SC03227F
dcterms.bibliographicCitation.url
http://pubs.rsc.org/en/Content/ArticleLanding/2015/SC/C4SC03227F#!divAbstract
refubium.affiliation
Biologie, Chemie, Pharmazie
de
refubium.mycore.fudocsId
FUDOCS_document_000000023580
refubium.resourceType.isindependentpub
no
refubium.mycore.derivateId
FUDOCS_derivate_000000005754
dcterms.accessRights.openaire
open access