Comprehensive mutational scanning of a kinase in vivo reveals substrate-dependent fitness landscapes.

ABSTRACT: Deep mutational scanning has emerged as a promising tool for mapping sequence-activity relationships in proteins, ribonucleic acid and deoxyribonucleic acid. In this approach, diverse variants of a sequence of interest are first ranked according to their activities in a relevant assay, and this ranking is then used to infer the shape of the fitness landscape around the wild-type sequence. Little is currently known, however, about the degree to which such fitness landscapes are dependent on the specific assay conditions from which they are inferred. To explore this issue, we performed comprehensive single-substitution mutational scanning of APH(3')II, a Tn5 transposon-derived kinase that confers resistance to aminoglycoside antibiotics, in Escherichia coli under selection with each of six s

SUBMITTER: Melnikov A 

PROVIDER: S-EPMC4132701 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature