Study paves way for a new approach to fight infections
With the help of a group of researchers who have gained new insight into the molecular mechanisms of living organisms, a new way to manage diseases may soon be possible.
The proliferating cell nucleus antigen (PCNA), is a protein that plays an important role in all aspects of DNA repair, replication, and recombination. The recruitment of DNA polymerases is an important step in DNA replication. Any method that targets PCNA can be used to block this step.
It is widely recognized as a therapeutic target because it is structural protein. Its structure is similar across species. However, a PCNA from one species may not be functional in another. This problem has been solved by the new study.
To understand cross-species incompatibility, the researchers started by analyzing the X-ray crystal structure (PCNA) of a red bread mold called Neurospora crassa. The researchers found that the interdomain connecting loop (IDCL), and J loop structures were significantly different among PCNAs.
They created mutants of Neurospora crassia PCNA to confirm that structural differences were indeed responsible for functional incompatibility. These mutants mimicked the IDCL and J loop structures found in Saccharomyces cerevisiae's PCNA. Genetic analysis showed that the mutants could function in Saccharomyces cerevisiae. The susceptibility to various genotoxic agents in the mutants harbouring ScPCNA was identical to yeast cells that express ScPCNA. It was evident that the structures of PCNA's J loop and IDCL were crucial determinants for interspecies functional compatibility.
India Science Wire was informed by scientists that their study had helped them understand the intricate interplay between PCNA and partner proteins in cells. This will allow us to develop therapeutic agents that target PCNA. This will allow us to make sure that drugs are species-specific.
Researchers from the Laboratory of Genomic Instability and Diseases and Laboratory of Macromolecular Crystallography, Department of Infectious Disease Biology at Institute of Life Sciences in Bhubaneswar conducted the study.
Dr. Narottam Acharya of ILS’s Laboratory of Genomic Instability and Diseases and Dileep Vasudevan of ILS’s Laboratory of Macromolecular Crystallography led the team. Rajivgandhi and Kodavati Sundaram were the other members. Their work was published in the Journal of Biological Chemistry.