Design of an allosterically modulated doxycycline and doxorubicin drug-binding protein.

ABSTRACT: The allosteric interplay between distant functional sites present in a single protein provides for one of the most important regulatory mechanisms in biological systems. While the design of ligand-binding sites into proteins remains challenging, this holds even truer for the coupling of a newly engineered binding site to an allosteric mechanism that regulates the ligand affinity. Here it is shown how computational design algorithms enabled the introduction of doxycycline- and doxorubicin-binding sites into the serine proteinase inhibitor (serpin) family member α1-antichymotrypsin. Further engineering allowed exploitation of the proteinase-triggered serpin-typical S-to-R transition to modulate the ligand affinities. These design variants follow strategies observed in naturally occurring pla

SUBMITTER: Schmidt K 

PROVIDER: S-EPMC5984491 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature