Edinburgh Research Explorer

A protein that looks like DNA! The fundemental interactions required for DNA mimicry

Project: Research

StatusFinished
Effective start/end date1/06/0331/05/06
Total award£164,929.00
Funding organisationBBSRC
Funder project reference15/C17860
Period1/06/0331/05/06

Description

We have solved the first structure of a protein that mimics B-form DNA. This structural mimicry enables it to inhibit totally the activity of an entire group of DNA-binding enzymes, the type I DNA restriction and modification enzymes.
We combined rigorous thermodynamic and kinetic approaches with protein engineering to determine how the DNA mimicry operates and to compare this novel mechanism with the normal DNA binding process of the R/M enzymes. An understanding of how DNA mimicry by proteins is achieved in structural, energetic and kinetic terms provides a foundation for the development of a new area of proteinaceous DNA mimics to produce research tools, diagnostic tests and, possibly, therapeutic materials.

Layman's description

We have solved the first structure of a protein that mimics B-form DNA. This structural mimicry enables it to inhibit totally the activity of an entire group of DNA-binding enzymes, the type I DNA restriction and modification enzymes.
We combined rigorous thermodynamic and kinetic approaches with protein engineering to determine how the DNA mimicry operates and to compare this novel mechanism with the normal DNA binding process of the R/M enzymes. An understanding of how DNA mimicry by proteins is achieved in structural, energetic and kinetic terms provides a foundation for the development of a new area of proteinaceous DNA mimics to produce research tools, diagnostic tests and, possibly, therapeutic materials.

Key findings

We have solved the first structure of a protein that mimics B-form DNA. This structural mimicry enables it to inhibit totally the activity of an entire group of DNA-binding enzymes, the type I DNA restriction and modification enzymes.
We combined rigorous thermodynamic and kinetic approaches with protein engineering to determine how the DNA mimicry operates and to compare this novel mechanism with the normal DNA binding process of the R/M enzymes. An understanding of how DNA mimicry by proteins is achieved in structural, energetic and kinetic terms provides a foundation for the development of a new area of proteinaceous DNA mimics to produce research tools, diagnostic tests and, possibly, therapeutic materials.
Our work was published in 10 research papers and inspired the company EPICENTRE to develop the mimic as a microbiological tool. The mimic has also been developed as an affinity tag for protein purification. The research papers have been cited over 300 times.

Research outputs