Monday, December 16, 2013

Scientists study essential enzyme to better understand molecular evolution

Scientists at the University of Iowa analyzed various forms of the enzyme dihydrofolate reductase (DHFR) using bioinformatics, computer-based calculations, artificial mutagenesis and kinetic measurements. The result of their work is published in the recent JBC paper entitled: 'Preservation of Protein Dynamics in Dihydrofolate Reductase Evolution'.

DHFR with dihydrofolate (left)
and NADPH (right) bound

The scientists chose DHFR due to its well characterized role and the fact that it is present in nearly all organisms. DHFR is involved in DNA biosynthesis and cell replication, therefore, it is essential to survival. Indeed, DHFR has been targeted in several therapeutic applications where antagonists have been used as anti-cancer treatments and anti-bacterial agents.

The results of the current paper showed that although bacteria and human DHFR are different in terms of genetic and protein sequence, the chemical conversion performed by this enzyme is quite well conserved. Indeed the bacterial enzyme already has reactants perfectly aligned in its active site! This was quite surprising as the human enzyme is not only genetically different but much faster.

The results of this work are important in the design of drugs against DHFR and the design of catalysts that are inspired by nature.

Some information for this blog was obtained from: 'Evolution On Molecular Level'

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