Chemical genetic inhibition of DEAD-box proteins using covalent complementarity.

ABSTRACT: DEAD-box proteins are an essential class of enzymes involved in all stages of RNA metabolism. The study of DEAD-box proteins is challenging in a native setting since they are structurally similar, often essential and display dosage sensitivity. Pharmacological inhibition would be an ideal tool to probe the function of these enzymes. In this work, we describe a chemical genetic strategy for the specific inactivation of individual DEAD-box proteins with small molecule inhibitors using covalent complementarity. We identify a residue of low conservation within the P-loop of the nucleotide-binding site of DEAD-box proteins and show that it can be mutated to cysteine without a substantial loss of enzyme function to generate electrophile-sensitive mutants. We then present a series of small molecu

SUBMITTER: Barkovich KJ 

PROVIDER: S-EPMC6158709 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature