Computational design of orthogonal nucleoside kinases.
We report the computational enzyme design of an orthogonal nucleoside analog kinase for 3'-deoxythymidine. The best kinase variant shows an 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.
Department of Chemistry, Emory University, Atlanta, GA 30322, USA.
Lingfeng
L
Liu
Paul
P
Murphy
David
D
Baker
Stefan
S
Lutz
D019295:Computational Biology; D008958:Models, Molecular; D009705:Nucleosides / Q000737:chemistry / Q000378:metabolism*; D010770:Phosphotransferases / Q000737:chemistry / Q000378:metabolism*; D013379:Substrate Specificity
D009705:Nucleosides; D010770:Phosphotransferases