Computational design of orthogonal nucleoside kinases

• Authors: Lingfeng Liu, Emory University; Paul Murphy, University of Washington; David Baker, University of Washington; Stefan Lutz, Emory University
• Journal Title: Chemical Communications
• Volume: Volume 46, Number 46
• Publisher: Royal Society of Chemistry | 2010-10-19, Pages 8803-8805
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1039/c0cc02961k
• Subjects: Chemistry, General; Chemistry, Biochemistry; Health Sciences, General

Abstract

We report the computational enzyme design of an orthogonal nucleoside analog kinase for 3’-deoxythymidine. The best kinase variant shows a 8500-fold change in substrate specificity, resulting from a 4.6-fold gain in catalytic efficiency for the nucleoside analog and a 2000-fold decline for the native substrate thymidine.