Selective inhibition of DNA replicase assembly by a non-natural nucleotide: exploiting the structural diversity of ATP-binding sites.

ABSTRACT: DNA synthesis is catalyzed by an ensemble of proteins designated the replicase. The efficient assembly of this multiprotein complex is essential for the continuity of DNA replication and is mediated by clamp-loading accessory proteins that use ATP binding and hydrolysis to coordinate these events. As a consequence, the ability to selectively inhibit the activity of these accessory proteins provides a rational approach to regulate DNA synthesis. Toward this goal, we tested the ability of several non-natural nucleotides to inhibit ATP-dependent enzymes associated with DNA replicase assembly. Kinetic and biophysical studies identified 5-nitro-indolyl-2'-deoxyribose-5'-triphosphate as a unique non-natural nucleotide capable of selectively inhibiting the bacteriophage T4 clamp loader versus the

SUBMITTER: Eng K 

PROVIDER: S-EPMC3169429 | biostudies-literature | 2010 Feb

REPOSITORIES: biostudies-literature