PRP2 Inhibitors

PRP2 inhibitors represent a chemical class that specifically targets the PRP2 protein, which is a critical component of the spliceosome, a macromolecular complex involved in pre-mRNA splicing. PRP2, also known as DHX16, is an ATP-dependent RNA helicase that facilitates the structural rearrangements required for the second step of splicing, where exons are joined together and introns are removed. The inhibition of PRP2 disrupts its function in this highly coordinated process, potentially leading to altered or incomplete splicing events. In particular, PRP2's activity depends on its ability to hydrolyze ATP to provide the necessary energy for helicase activity, which allows the unwinding and remodeling of RNA-protein complexes. Compounds classified as PRP2 inhibitors typically interact with this protein by either blocking ATP binding or by interfering with its helicase function, ultimately modulating RNA processing at the molecular level.

The detailed mechanism of PRP2 inhibition often involves the stabilization of specific conformations of the spliceosome or the prevention of required transitions between different structural states during the splicing cycle. These inhibitors are frequently small molecules designed to target the ATPase domain or interact with key residues involved in RNA binding. Structural studies, often involving X-ray crystallography or cryo-electron microscopy, have been used to map the interaction sites between PRP2 and its inhibitors. Such interactions can result in the stalling of spliceosome assembly or improper coordination of splicing intermediates, leading to the failure of pre-mRNA to undergo accurate splicing. As PRP2 is part of a complex network of helicases and splicing factors, inhibitors of this protein can provide valuable insights into RNA-protein interactions and the energy-dependent dynamics of spliceosome assembly and disassembly. These compounds serve as molecular probes that deepen our understanding of RNA splicing fidelity and regulation at a structural and biochemical level.