Proposal of Chemical Inhibitors That Compete with the Binding of RNA Polymerase II Subunits to Essential GTPases GPN Npa3 and Gpn1.

ABSTRACT: The Gpn1, Gpn2, and Gpn3 proteins are members of the GTPase GPN family; yeast Npa3 is an orthologue of the human Gpn1 protein. These proteins play a crucial role in the nuclear accumulation of RNA polymerase II, functioning as molecular chaperones. The crystallographic structures of Npa3 reveal open and closed conformations, which are dependent on the bound guanine nucleotide (GMPPCP or GDP, respectively). The open conformation of Npa3 exhibits a hydrophobic pocket proposed to be essential for the recognition and binding of specific peptides of RNA polymerase II, contributing to its biogenesis; however, structural data on these complexes remain unavailable. In this work, we present in silico models of the interactions between the crystallographic structure of monomeric Npa3 in its o

SUBMITTER: Muniz-Luna JA 

PROVIDER: S-EPMC12612918 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature